Dynamics of heart rate response in sleeping infants exposed to tone stimuli

Heart rate, EEG, and motor responses were recorded following presentation of a series of 6–10 sound stimuli (2.5-s tones of 1000, 4000, and 250 Hz, 70 dB, interstimulus intervals 18–25 s) in neonates aged 9 to 22 weeks during stage 2–3 sleep. The infants (17 of 19) revealed heart rate (HR) changes in response to tone stimuli that consisted in an expanded form of three phases: (1) short-latency (at 1 s after tone presentation) HR deceleration, (2) HR acceleration with a maximum at 3–5 s, and (3) late HR deceleration at 6–9 s of the poststimulus interval. The occurrence rate of the first two phases of cardiac response is relatively constant during a series of stimuli, whereas the likelihood of late HR deceleration is the highest following the first tone presentation and decreases significantly when the stimulus is repeated. Differences in the dynamics and statistical analysis allow a relative independence of all the three response phases to be suggested. The HR acceleration phase is dramatically enhanced in association with the motor response elicited by the sound stimulus. The late HR deceleration phase occurs not only after the first presentation of stimuli, but also when they are repeated if they evoke EEG reaction (vertex potentials) in response to both the beginning and end of the tone sound. Possible mechanisms of the three phases of poststimulus HR changes are: the vagal cardiac reflex associated with the acoustic (adaptive) reflex, activation of sympathetic efferents in combination with the startle reflex, and secondary vagal deceleration of sinus rhythm likely to be associated with the processes of perception (detection) of a “novel” stimulus and to serve as an indirect sign of an orienting reaction.     

Intracardiac neurogenic regulation of the rate of excitation conduction in the atrioventricular area of the heart. I. Dependence of the effect on the moment of stimulus application in spontaneous and artificially stabilized rhythms of the heart beat

The influence of the intracardiac reflectory system on the atrioventricular propagation in the experiments on the isolated frog's heart has been investigated. The ability of the intracardiac reflectory cholinergic activation to accelerate or reduce the atrioventricular propagation was confirmed. Both effects remain on the background of the artificially stabilized heart rhythm. The dromotropic effect direction was shown not to be connected with the electrocardiogram (ECG) phase at which the stimulus has been given; the positive or negative dromotropic effect can appear giving the stimulus at the same phase of the ECG. But there is a strong correlation between the moment of the stimulation and the dromotropic effect intensity. The most high degree of the acceleration and inhibition appears when the stimulus is given near the P component of the ECG.     

Postnatal development of heart rate patterns elicited by an aversive CS and US in cats

Heart rate and motor responses were recorded in cats of different ages during classical conditioning. A deceleratory-acceleratory heart rate pattern observed during the CS-US interval in one- and four-week-old kittens is an alpha conditioned response, a potentiated original response to the CS. At eight weeks of age two new distinct patterns of pure acceleration or pure deceleration are acquired during conditioning and in the absence of motor learning. At 12 weeks of age and in adult subjects, heart rate patterns during the CS-US interval become more complex and conditioned motor responses can be observed. A covariance of HR acceleration and motor responses during the CS-US interval is absent in eight-week-old subjects, but quite high in 12-week-old subjects and adult cats. The data are interpreted as suggesting separate elicitatory mechanisms of HR and motor responses which may show synchrony later in ontogeny.     

Executive functioning in attention-deficit/hyperactivity disorder: questioning the notion of planning deficits with heart rate reactivity

This study employed a paired stimulus paradigm to compare phasic changes in heart rate among children (age categories 6–8, 9–10, and 11–12) and adults (age categories 18–19 and 20–22) with attention-deficit/hyperactivity disorder (ADHD) and age-matched controls. A sample of 95 participants (19 ADHD-diagnosed children, 34 controls, 20 ADHD-diagnosed adults, and 22 controls) solved a planning task, the Tower of London, through 4 levels of difficulty. It was hypothesized that groups with ADHD would show greater heart rate acceleration and less final deceleration than would controls, and that these heart rate responses would change with age and difficulty level as well. Though heart rate differences were found among age categories and difficulty levels, none were found between participants with ADHD and controls. The lack of ADHD differences are not consistent with the behavioral evidence that planning by itself is one of the marked executive function deficits in ADHD. Because ADHD differences were not evident, the effects either were not present or were smaller than that of difficulty level and age. Possible explanations for this lack of difference and future directions are discussed.     

Effects of fetal behavioral states on renal sympathetic nerve activity and arterial pressure of unanesthetized fetal sheep

Fetal behavior, renal sympathetic nerve activity (RSNA), mean arterial pressure (MAP), and heart rate (HR) were studied 1-3 days after surgery in seven fetal sheep (aged 127-136 days). Five behavioral states were defined from chart recordings of electrocortical (electrocorticographic; ECoG) activity and eye, limb, and breathing movements. Most records were of high-voltage ECoG (HV) or low-voltage (LV) ECoG with breathing (LVB); 6.7 +/- 1.7% were LV ECoG with no breathing (LV0). RSNA was lower in LV0 (P < 0.001) and greater in LVB than in HV (P < 0.05). MAP was lower in both LV states than in HV and when the fetuses went from LV to HV (P < 0.001 to P < 0.03). HR was highest in HV (P < 0.001). In HV and LVB and when the fetus went from LV to HV, MAP and HR were inversely related (P = 0.012-0.003). In LVB and from LV to HV there were direct relationships between MAP and RSNA (P = 0.0014, P = 0.08), and when the fetus went from LV to HV there was also an inverse relationship between HR and RSNA (P = 0.02). Thus fetal RSNA, MAP, and HR are affected by behavioral state as is fetal cardiovascular control. The increase in RSNA during fetal breathing showed that there was an altered level of fetal RSNA associated with fetal breathing activity.     

Using Psychophysiological Measures to Examine the Temporal Profile of Verbal Humor Elicitation

Despite its pervasiveness in popular culture, there remains much to be learned about the psychological and physiological processes that underlie our experience of humor. In the present study, we examined the temporal profile of verbal humor elicitation using psychophysiological measures of heart rate (HR) and facial electromyography (EMG). Consistent with recent prior research on cardiovascular changes to perceived humor, we found that HR acceleration was greater for jokes relative to non-jokes, and was positively related to the level of perceived humor elicited by these jokes. In addition, activity recorded from the zygomaticus major muscle that controls smiling was found to be greater for jokes relative to non-jokes. To link these physiological changes to the psychological processes that govern humor comprehension, we took the initial inflection point of the zygomatic EMG response as a marker for the onset of humor comprehension, and used this marker to probe the pattern of cardiovascular activity at this time-point. We estimated the onset of the humor response to occur during the initial HR deceleration phase, and found that jokes relative to non-jokes elicited a decreased HR response at this time-point. This result questions the previously forwarded notion that the psychological “moment of insight” that signals the start of the humor response is always associated with heightened cardiovascular activity. This discrepancy is discussed in relation to possible differences in the cognitive processes required to comprehend different forms of humor. At a broader level, our results also demonstrate the advantages of combining different psychophysiological measures to examine psychological phenomena, and illustrate how one such measure can constrain the interpretation of others.     

Baroreceptor reflex and arterial rigidity in schoolchildren

In this work there is shown a variability of heart rate and time delay of pulse wave of main arteries in schoolchildren.There is used the function of ordinary coherence of HR and DPW (time delay of pulse wave). This function reflects the rate of statistical linear relation of two processes in heart and blood vessels. A high tone of sympathetic part of vegetative nervous activity in schoolchildren increases CO (cardeiac out), shortens the hard connection phase of HR and DPW and results in a new system characteristic--arterial rigidity. There are presented results of passive orthostatic test and pharmacological tests on activation of sympathetic part of vegetative nervous activity in schoolchildren with heart rate problems.     

Differential cardiorespiratory control elicited by activation of ventral medullary sites in mice.

We studied the respiratory and blood pressure responses to chemical stimulation of two regions of the ventral brainstem in mice: the rostral and caudal ventrolateral medulla (RVLM and CVLM, respectively). Stimulation of the RVLM by microinjections of the excitatory amino acid L-glutamate induced increases in diaphragm activity and breathing frequency, elevation of blood pressure (BP), and a slight increase in heart rate (HR). However, activation of the CVLM induced a decrease in breathing frequency, mainly due to prolongation of expiratory time (TE), and hypotension associated with a slight slowing of HR. Because adrenergic mechanisms are known to participate in the control of respiratory timing, we examined the role of alpha(2)-adrenergic receptors in the RVLM region in mediating these inhibitory effects. The findings demonstrated that blockade of the alpha(2)-adrenergic receptors within the RVLM by prior microinjection of SKF-86466 (an alpha(2)-adrenergic receptor blocker) significantly reduced changes in TE induced by CVLM stimulation but had little effect on BP responses. These results indicate that, in mice, activation of the RVLM increases respiratory drive associated with an elevation of BP, but stimulation of CVLM induces prolongation of TE via an alpha(2)-adrenergic signal transduction pathway.     

Leydig neuron activity modulates heartbeat in the medicinal leech

1. Leydig neurons fire spontaneously at low rates (less than 4 Hz), but their activity increases with mechanical stimulation or electrical stimulation of mechanosensory neurons. These conditions also cause acceleration of bursting in heart motor neurons. 2. The firing rate of Leydig cells was found to regulate heart rate in chains of isolated ganglia. When Leydig neurons were made to fire action potentials at relatively high frequencies (ca. 5-10 Hz), however, heart motor neurons ceased bursting and were either silenced or fired erratically. 3. Firing of Leydig neurons at high rates caused bilateral heart interneurons of ganglia 3 or 4 to fire tonically rather than in their normal alternating bursts Tonic firing of these heart interneurons accounts for the prolonged barrages of ipsps recorded in heart motor neurons and the disruption of their normal cyclic activity. 4. Preventing spontaneous activity of Leydig neurons with injected currents in isolated ganglia caused deceleration of the heartbeat rhythm but did not halt oscillation. 5. Electrical stimulation of peripheral nerve roots with Leydig neuron activity suppressed in isolated ganglia caused acceleration of heart rate.     

Cardiac sympathetic nerve stimulation does not attenuate dynamic vagal control of heart rate via alpha-adrenergic mechanism

Complex sympathovagal interactions govern heart rate (HR). Activation of the postjunctional beta-adrenergic receptors on the sinus nodal cells augments the HR response to vagal stimulation, whereas exogenous activation of the presynaptic alpha-adrenergic receptors on the vagal nerve terminals attenuates vagal control of HR. Whether the alpha-adrenergic mechanism associated with cardiac postganglionic sympathetic nerve activation plays a significant role in modulation of the dynamic vagal control of HR remains unknown. The right vagal nerve was stimulated in seven anesthetized rabbits that had undergone sinoaortic denervation and vagotomy according to a binary white-noise signal (0-10 Hz) for 10 min; subsequently, the transfer function from vagal stimulation to HR was estimated. The effects of beta-adrenergic blockade with propranolol (1 mg/kg i.v.) and the combined effects of beta-adrenergic blockade and tonic cardiac sympathetic nerve stimulation at 5 Hz were examined. The transfer function from vagal stimulation to HR approximated a first-order, low-pass filter with pure delay. beta-Adrenergic blockade decreased the dynamic gain from 6.0 +/- 0.4 to 3.7 +/- 0.6 beats x min(-1) x Hz(-1) (P < 0.01) with no alteration of the corner frequency or pure delay. Under beta-adrenergic blockade conditions, tonic sympathetic stimulation did not further change the dynamic gain (3.8 +/- 0.5 beats x min(-1) x Hz(-1)). In conclusion, cardiac postganglionic sympathetic nerve stimulation did not affect the dynamic HR response to vagal stimulation via the alpha-adrenergic mechanism.     

Selective impairment of central mediation of baroreflex in anesthetized young adult Fischer 344 rats after chronic intermittent hypoxia

Baroreflex control of heart rate (HR) is impaired after chronic intermittent hypoxia (CIH). However, the location and nature of this response remain unclear. We examined baroreceptor afferent, vagal efferent, and central components of the baroreflex circuitry. Fischer 344 (F344) rats were exposed to room air (RA) or CIH for 35-50 days and were then anesthetized with isoflurane, ventilated, and catheterized for measurement of mean arterial blood pressure (MAP) and HR. Baroreceptor function was characterized by measuring percent changes of integrated aortic depressor nerve (ADN) activity (Int ADNA) relative to the baseline value in response to sodium nitroprusside- and phenylephrine-induced changes in MAP. Data were fitted to a sigmoid logistic function curve. HR responses to electrical stimulation of the left ADN and the right vagus nerve were assessed under ketamine-acepromazine anesthesia. Compared with RA controls, CIH significantly increased maximum baroreceptor gain or maximum slope, maximum Int ADNA, and Int ADNA range (maximum - minimum Int ADNA), whereas other parameters of the logistic function were unchanged. In addition, CIH increased the maximum amplitude of bradycardic response to vagal efferent stimulation and decreased the time from stimulus onset to peak response. In contrast, CIH significantly reduced the maximum amplitude of bradycardic response to left ADN stimulation and increased the time from stimulus onset to peak response. Therefore, CIH decreased central mediation of the baroreflex but augmented baroreceptor afferent function and vagal efferent control of HR.     

Differentiating Orienting and Defensive Responses to Concealed Information: The Role of Verbalization

Using physiological measures, concealed information can be validly assessed. Orienting theory has been proposed to account for concealed information testing. As orienting is characterized by heart rate deceleration, one would expect this type of heart rate response to concealed information. However, with some exceptions, an initial heart rate acceleration to concealed information is typically observed. In the present paper, we examine the role of verbalization to explain the mixed pattern of heart rate changes. Using a within-subjects design, 30 participants were asked to either remain silent or to give an overt verbal response (“yes”/”no”) to concealed autobiographical and control information. The results indicate that verbalization accounts for the initial heart rate acceleration. In line with the orienting theory, initial heart rate deceleration is observed when participants remained silent. Bruno Verschuere is a postdoctoral fellow of the Scientific Research Foundation (FWO).     

Heart and ventilatory measures in crayfish during environmental disturbances and social interactions

Most animals assess the environment in which they live and alter their behavior according to various stimuli. When the animal does not make significant behavioral changes, as measured by bodily movements, the animal may be characterized as unresponsive to a given stimulus. This study demonstrates that when behavioral movements of crayfish cannot be observed, physiological measures of heart rate (HR) and ventilatory rate (VR) show dramatic changes in response to defined sensory stimuli. In the majority of cases, upon anticipation of a social interaction with another crayfish both HR and VR will increase. During an agonistic encounter between two crayfish, the level of HR and VR correlate with the intensity of the interaction. Such rapid responses in cardiac and respiratory systems to environmental disturbances and anticipation of a social interaction suggest an autonomic-like regulation associated with fear, flight or fight. Since behavioral observations do not allow an internal status to be readily assessed, we suggest that HR and VR may serve as a useful bioindex in crustaceans to their internal drive or possibly an awareness level to environmental cues.     

Cardiac,respiratory, and motor activity in norm and after activation of catecholaminergic systems in newborn rat pups

Study of parameters of the cardiac, respiratory, and motor activity (MA) was carried out on newborn rat pups for the first day after birth (P0) and at the 14th day of postnatal development (P14) after change of the activity levels of dopaminergic and noradrenergic systems. To provide an excessive level of catecholamines, the animals were administered individually with L-DOPA (25–100 mg/kg) and with the indirect adrenomimetic isoamine (3 and 10 mg/kg). Additionally there were studied effects of L-DOPA and isoamine after blockade of D1 and D2 dopamine receptors (antagonists SCH-23390 and sulpirid). The L-DOPA administration produced a dose-dependent MA enhancement with its subsequent possible conversion into the continuous generalized activity. At P0 the release of monoamines was accompanied by development of weak bradycardia. There was noted a tendency for acceleration of respiration at administration of the low dose both of L-DOPA and of isoamine and for its deceleration at high doses. At P14 the L-DOPA administration was accompanied by deceleration of the heart rate (HR) by 8% and by acceleration of respiration rate (RR) by 26%. The isoamine administration produced an insignificant decrease of HR and an increase of RR by 8% at the low dose and by 21% at the high dose of the agent. At the blockade of D1 receptors, RR remained close to the background values, while at the blockade of D2 receptors it decreased insignificantly. Blockade of D1 and D2 receptors did not cause significant HR changes. Analysis of the HR variability has shown that both after L-DOPA administration and at blockade of dopamine receptors no unidirectional reaction was observed: in 80% of rat pups the portion of nerve mechanisms of HR regulation increased, while in the rest-of sympathetic and humoral factors at a decrease of parasympathetic effects. In all rat pups the isoamine administration was accompanied by a shift of the specter power into the higher frequency area; in 60% of the animals there were enhanced sympathetic effects. At P14 in rat pups after administration both of L-DOPA and of isoamine, the sympathetic nervous effects were predominant. Thus, at P0 both at release of endogenous catecholamines and at their excessive concentration in rat pups there occurs a qualitative change of character of the catecholaminergic effects on functional activity of excitable structures, particularly of those connected with regulation of respiration.     

Peculiarities of Ca2+ regulation of functional activity of myocardium of frog Rana temporaria

To elucidate role of intra- and extracellular Ca2+ in regulation of rhythm and strength of frog heart contractions, there were studied ECC and isometric contraction of myocardium preparations in response to verapamil, adrenaline, and blockers of alpha- and beta-adrenoreceptors. It has been shown that after an intramuscular injection of verapamil (6 mg/kg), bradycardia develops, the heart rate (HR) decreasing by 50-70 %. Further, the cardiac arrest occurred; however, administration to the animals of adrenaline (100 mg/kg) restored the cardiac rhythm for a short while. After an intramuscular injection of adrenaline at doses of 0.1-10 mg/kg, no essential changes were observed in the potential action amplitude and HR; an increase of the administered adrenalin concentration to 100 mg/kg was not accompanied by the cardiac rhythm stimulation, as this takes place in homoiothermal animals and human; on the contrary, an essential HR deceleration was revealed. Phentolamine (5 mg/kg) gradually decelerated HR rhythm by 32-45 %. The potential amplitude changed insignificantly. A subsequent intracardiac injection of adrenaline (100 mg/kg) on the background of block of alpha-adrenoreceptors produced acceleration of the rhythm (by 13-21%) and fall of the electrogram amplitude. These results can indicate that in the frog heart, phentolamine interacts predominanty with alpha-adrenoreceptors. An intracardiac administration of propranolol (1 mg/kg) to frogs promoted inhibition of beta-adrenergic receptors and produced a gradual cardiac rhythm deceleration. In experiments on assessment of verapamil effect on the character of contractions this preparation at a concentration of 150 microM was established to produce a significant dosedependent decrease of the contraction strength. A rise of verapamil concentration in the sample to 200 microM led to a decrease of the amplitude, on average, by 68-70 % and in individual preparations -- by 80-85 %; however, administration into the sample of adrenaline (10 microM) restored the cardiac contraction strength. Adrenaline (1 nM--100 microM) increased markedly the contraction amplitude. Phentolamine (10 microM) did not inhibit transmission of contractile signal to cardiomyocytes; this was manifested in that the contraction amplitude after addition of adrenaline (10 microM) into the sample was approximately the same as in the sample containing no phentolamine. Propranolol (10 microM) eliminated the stimulatory action of adrenaline (10 microM). The results of these experiments indicate that in the frog ventricular cardiomyocytes the main adrenaline acceptors are beta-adrenoreceptors.     

Parasympathetic Stimuli on Bronchial and Cardiovascular Systems in Humans

Background

It is not known whether parasympathetic outflow simultaneously acts on bronchial tone and cardiovascular system waxing and waning both systems in parallel, or, alternatively, whether the regulation is more dependent on local factors and therefore independent on each system. The aim of this study was to evaluate the simultaneous effect of different kinds of stimulations, all associated with parasympathetic activation, on bronchomotor tone and cardiovascular autonomic regulation.

Methods

Respiratory system resistance (Rrs, forced oscillation technique) and cardio-vascular activity (heart rate, oxygen saturation, tissue oxygenation index, blood pressure) were assessed in 13 volunteers at baseline and during a series of parasympathetic stimuli: O₂ inhalation, stimulation of the carotid sinus baroreceptors by neck suction, slow breathing, and inhalation of methacholine.

Results

Pure cholinergic stimuli, like O₂ inhalation and baroreceptors stimulation, caused an increase in Rrs and a reduction in heart rate and blood pressure. Slow breathing led to bradycardia and hypotension, without significant changes in Rrs. However slow breathing was associated with deep inhalations, and Rrs evaluated at the baseline lung volumes was significantly increased, suggesting that the large tidal volumes reversed the airways narrowing effect of parasympathetic activation. Finally inhaled methacholine caused marked airway narrowing, while the cardiovascular variables were unaffected, presumably because of the sympathetic activity triggered in response to hypoxemia.

Conclusions

All parasympathetic stimuli affected bronchial tone and moderately affected also the cardiovascular system. However the response differed depending on the nature of the stimulus. Slow breathing was associated with large tidal volumes that reversed the airways narrowing effect of parasympathetic activation.     

The marine mammal dive response is exercise modulated to maximize aerobic dive duration

When aquatically adapted mammals and birds swim submerged, they exhibit a dive response in which breathing ceases, heart rate slows, and blood flow to peripheral tissues and organs is reduced. The most intense dive response occurs during forced submersion which conserves blood oxygen for the brain and heart, thereby preventing asphyxiation. In free-diving animals, the dive response is less profound, and energy metabolism remains aerobic. However, even this relatively moderate bradycardia seems diametrically opposed to the normal cardiovascular response (i.e., tachycardia and peripheral vasodilation) during physical exertion. As a result, there has been a long-standing paradox regarding how aquatic mammals and birds exercise while submerged. We hypothesized based on cardiovascular modeling that heart rate must increase to ensure adequate oxygen delivery to active muscles. Here, we show that heart rate (HR) does indeed increase with flipper or fluke stroke frequency (SF) during voluntary, aerobic dives in Weddell seals (HR?=?1.48SF?-?8.87) and bottlenose dolphins (HR?=?0.99SF?+?2.46), respectively, two marine mammal species with different evolutionary lineages. These results support our hypothesis that marine mammals maintain aerobic muscle metabolism while swimming submerged by combining elements of both dive and exercise responses, with one or the other predominating depending on the level of exertion.     

Respiratory muscle responses elicited by dorsal periaqueductal gray stimulation in rats

The periaqueductal gray matter is an essential neural substrate for central integration of defense behavior and accompanied autonomic responses. The dorsal half of the periaqueductal gray matter (dPAG) is also involved in mediating emotional responses of anxiety and fear, psychological states that often are associated with changes in ventilation. However, information regarding respiratory modulation elicited from this structure is limited. The present study was undertaken to investigate the relationship between stimulus frequency and magnitude on ventilatory pattern and respiratory muscle activity in urethane-anesthetized, spontaneously breathing rats. Electrical stimulation in the dPAG-recruited abdominal muscle activity increased ventilation and increased respiratory frequency by significantly shortening both inspiratory time and expiratory time. Ventilation increased within the first breath after the onset of stimulation, and the respiratory response increased with increasing stimulus frequency and magnitude. dPAG stimulation also increased baseline EMG activity in the diaphragm and recruited baseline external abdominal oblique EMG activity, normally quiescent during eupneic breathing. Significant changes in cardiorespiratory function were only evoked by stimulus intensities >10 microA and when stimulus frequencies were >10 Hz. Respiratory activity of both the diaphragm and abdominal muscles remained elevated for a minimum of 60 s after cessation of stimulation. These results demonstrate that there is a short-latency respiratory response elicited from the dPAG stimulation, which includes both inspiratory and expiratory muscles. The changes in respiratory timing suggest rapid onset and sustained poststimulus dPAG modulation of the brain stem respiratory network that includes expiratory muscle recruitment.     

Spinal cord stimulation affects the central mechanisms of regulation of heart rate

The effect of spinal cord stimulation (SCS) on heart rate (HR) was studied in 25 patients without cardiological symptoms, who were undergoing SCS for various reasons. HR at rest significantly decreased during SCS. Physiological and pharmacological maneuvers of sympathetic and parasympathetic activation or blockade before and during SCS indicate that SCS interferes with the central mechanisms of regulation of HR mainly by inducing a functional sympathectomy, and that such an effect is mediated by an action on spinal cord ascending fibers.     

Cyclic 3'',5'' AMP relay in Dictyostelium discoideum. II. Requirements for the initiation and termination of the response

The secretion of 3H-cyclic adenosine 3',5'-monophosphate (cAMP) by prelabeled and suitably differentiated Dictyostelium discoideum amoebae was elicited in a perfusion apparatus by 10(-10) to 10(-5) M [14C]cAMP stimuli of defined magnitude and duration. Exogenous stimuli evoked an immediate increase in the rate of [3H]cAMP secretion which accelerated continuously to reach a peak of up to 100 times the unstimulated rate after 2--3 min of stimulation. Withdrawal of the stimulus at any time during the response led to a rapid decline to basal levels. Furthermore, a spontaneous decline in secretion rate was observed during prolonged cAMP stimulation, with a return to basal levels after 3--8 min of stimulation. After the initial secretory event, cells did not respond further to the continued presence of external [14C]cAMP unless (a) it was interrupted by a brief recovery period or (b) the level of the stimulus was increased sufficiently. Since the second increment could follow the first at any time, continuous secretion of [3H]cAMP could be sustained for up to 30 min by progressively increasing the stimulus between 10(-10) and 10(-5) M cAMP. The total magnitude of spontaneously terminated responses depended on the size of the increment in applied cAMP, larger stimuli evoking both a more rapid acceleration and a slower deceleration in [3H]cAMP secretion rate. The integrated response to a given increment in stimulus level was apparently independent of its "shape" - i.e., the duration, magnitude, and number of sub-steps in the increment. These data support two mechanistic inferences: that amoebae respond in proportion to relative increases in extracellular cAMP concentration, but adapt to the concentration of cAMP itself. The data further suggest that the initiation and termination of the response are mediated by cellular component(s) beyond cAMP-occupied receptors.