Sympathoadrenergic regulation and the adrenoceptor system

We investigated the effects of endurance and high-intensity training periods on the plasma catecholamine (CA) concentration at rest; on the basal alpha- and beta-adrenoceptor density, regulation, and function on circulating cells; and on the cardiovascular adaptation in long-distance runners and swimmers. The findings of each period were compared with those of untrained men. Endurance training of the long-distance runners and the swimmers led both to a reduced sympathetic activity at rest, indicated by lower CA values, and to a lower beta-receptor density and responsiveness on circulating lymphocytes and an increased alpha 2-receptor sensitivity on circulating platelets. During the high-intensity training period beta-receptor density and responsiveness increased, alpha 2-receptor sensitivity normalized, and heart rate as well as blood pressure values increased in both trained groups. The basal sympathetic activity remained reduced, but the norepinephrine-to-epinephrine (NE/EPI) ratio increased. The NE/EPI ratio might play an important part in the regulation of adrenoceptor density during these different training periods. Swimming-specific characteristics caused different physiological impacts compared with running training, but an attenuated baroreceptor sensitivity might be indicated in both intensively trained groups.     

Muscle fiber types and size in trained and untrained muscles of elite athletes

Tissue samples were obtained from vastus lateralis and deltoid muscles of physical education students (n = 12), Greco-Roman wrestlers (n = 8), flat-water kayakers (n = 9), middle- and long-distance runners (n = 9), and olympic weight and power lifters (n = 7). Histochemical stainings for myofibrillar adenosinetriphosphatase and NADH-tetrazolium reductase were applied to assess the relative distribution of fast-twitch and slow-twitch (ST) muscle fiber types and fiber size. The %ST was not different in the vastus (mean SD 48 +/- 14) and deltoid (56 +/- 13) muscles. The %ST was higher (P less than 0.001), however, in the deltoid compared with vastus muscle of kayakers. This pattern was reversed in runners (P less than 0.001). The %ST of the vastus was higher (P less than 0.001) in runners than in any of the other groups. The %ST of the deltoid muscle was higher in kayakers than in students, runners (P less than 0.001), and lifters (P less than 0.05). The mean fiber area and the area of ST fibers were greater (P less than 0.01) in the vastus than the deltoid muscle. Our data show a difference in fiber type distribution between the trained and nontrained muscles of endurance athletes. This pattern may reflect the adaptive response to long-term endurance training.     

Aerobic and anaerobic training effects on the antioxidant enzymes of the blood.

The purpose of the present study was to investigate the effects of aerobic and anaerobic training on serum lipid peroxidation levels and on antioxidant enzyme activities. Long distance runners for aerobic training group, and wrestlers for anaerobic training group were chosen. Non-sporting men were used as control group. When the aerobic power was compared; indirect VO2max of long-distance runners were found higher than wrestlers and control group (p<0.001, p<0.001). When lipid peroxidation levels were compared; levels of the thiobarbituric acid reactive substances (TBARS) of long distance runners were found to be lower than those in the control group (p<0.05), but similar to those found in wrestlers. Comparison of antioxidant enzyme activities in erythrocytes show that there were no significant difference among the groups in superoxide dismutase enzyme activities, but glutathione peroxidase (GPx) activity of long distance runners was higher than that measured in wrestlers (p<0.05). These results suggest that aerobic training increased in erythrocytes GPx activity with a subsequent decrease in plasma TBARS levels but anaerobic training had no effect on this process.     

Fluid conservation in athletes: responses to water intake, supine posture, and immersion

The roles of antidiuretic hormone (ADH) and aldosterone in the elicited diuretic responses of trained and untrained men to seated, supine, and head-out water immersed conditions were studied. Volunteers were comprised of groups of six untrained individuals, six trained swimmers, and six trained runners. Each subject underwent three protocols, six hours in a seated position, supine position, or immersion (35 degrees C water). The last two protocols were preceded and followed by 1 h of seated position. After 10 h of fasting, 0.5% body wt of water was drunk. One hour later the trained groups had higher urine osmolalities (P less than 0.05) and urinary excretion rates of ADH (P less than 0.05) and lower urine flow rates (P less than 0.05) than untrained subjects. Throughout the sitting protocol, urinary ADH was also higher in both trained groups (P less than 0.05). Both supine posture and immersion resulted in significant decreases in urinary ADH in the untrained subjects (P less than 0.05) but no changes wer noted in swimmers and only during the second hour of immersion in the runners (P less than 0.05). The natriuresis and kaliuresis were greater during immersion than in the supine position but plasma renin activity, measured only in trained groups, and plasma aldosterone, measured in the untrained group, were decreased similarly with both protocols. The increases in urinary sodium excretion and urine flow rate were lower in trained than untrained subjects during the supine and immersion protocols (P less than 0.05). The data are compatible with an increased osmotic but decreased volume sensitivity of ADH control in trained men.     

Cold tolerance of long-distance runners and swimmers in Hawaii

The purpose of this study was to measure thermal and metabolic responses of six marathon runners and six long-distance ocean swimmers during a standard cold tolerance test, and to compare the results. The two groups of lean endurance athletes lived in Hawaii and were matched on the basis of age, height, weight, and skinfold thickness. Maximal oxygen uptake, however, was significantly higher in the runners (66.5 versus 58.8 ml/(kg·min) for the swimmers). There were no significant differences in maximal tissue insulation or the derived nonfat insulation, although the runners tended to have higher values. Our findings suggest a possible hypothermic insulative adaptation in the runners and, therefore, indirectly support a recent hypothesis that marathon training may potentiate cross-adaptation to cold. Reasons for a relatively high nonfat insulation in the runners (0.098 (°C.m²)/W) are unknown, but seem related to a vascular mechanism.     

Autonomic degeneration and altered blood pressure control in humans

The study of patients with partial or total defects of their sympathetic nerves can help clarify the role of the sympathetic nervous system in blood pressure control. Denervation supersensitivity of both beta and alpha receptors develops in humans and is proportional to the degree of sympathetic withdrawal. Although alterations in beta-receptor sensitivity are familiar responses to beta agonists or antagonists, patients with decreased norepinephrine (NE) levels appear to develop alpha-receptor supersensitivity of greater hemodynamic importance. When beta supersensitivity is marked, there may be a pressor response to beta blockade even when circulating levels of NE and epinephrine are very low. Indomethacin blocks prostaglandin synthesis and causes an increase in blood pressure in patients with partial autonomic neuropathies. The drug increases blood pressure by enhancing alpha- and diminishing beta-receptor sensitivity to NE, so it is effective only in patients who have some residual NE release.     

Changes in serum proteins,-iron and -copper in swimmers before and after altitude training (author's transl)]

Fifteen male swimmers (mean age 19.3 +/- 2.1 years) were subjected to a standard 120 min swimming exercise test: a) before, and b) after 5 weeks of intensive training at middle altitude (2000 m). At rest, serum levels of alpha2-macroglobulin, transferrin and copper were elevated in swimmers as compared to untrained subjects. After the altitude training program, significant increases of the parameters of iron and copper metabolism, as well as of alpha2HS-glycoprotein and beta1A-globulin were observed. After the first exercise test (a), a significant rise in serum alpha1-acid glycoprotein, alpha1-antitrypsin, hemopexin, alpha2-macroglobulin, ceruloplasmin, transferrin, iron, copper and alpha2-HS-glycoprotein was noted. The same 120 min-exercise test after the altitude training (b) led to only small changes, especially as concerns the parameters of iron metabolism. The characteristic immediate and long-lasting changes in serum proteins and heavy metals in swimmers and the effects of training in middle altitude on the answer of the organism to swimming exercise with respect to the mentioned biochemical parameters are discussed.     

Serum and urinary markers of skeletal muscle tissue damage after weight lifting exercise

The purpose of this study was to determine whether high intensity weight lifting exercise produces elevations of urinary 3-methylhistidine (3-MH), serum creatine kinase activity (CK), and serum myoglobin concentration (MY), and whether trained weight lifters differed in such responses when compared to a group of untrained subjects. Ten experienced male weight lifters (EWL) and seven untrained male subjects (IWL) performed three sets of six weight lifting exercises at 70%-80% of 1 RM. All subjects consumed a meat-free diet. The 3-MH:creatinine (3-MH:CR) values decreased 24 h and 48 h following exercise (P less than 0.05). The 12-h and 24-h postexercise CK response and the 12-h postexercise MY response increased for both EWL and IWL (P less than 0.05). However, EWL had a lower 24-h postexercise CK response and lower 12-h and 24-h postexercise MY responses compared to IWL (P less than 0.05). Within 48 h following weight lifting exercise, skeletal muscle protein degradation (as assessed by 3-MH:CR values) decreased regardless of prior training experience whereas skeletal muscle tissue damage (as assessed by CK and MY responses) increased. However, prior weight lifting training appeared to diminish the extent of muscle tissue damage.     

Alpha 1- and beta-adrenergic receptors in brown adipose tissue of lean (Fa/?) and obese (fa/fa) Zucker rats. Effects of cold-acclimation,sucrose feeding and adrenalectomy.

1. The populations of alpha 1- and beta-adrenergic receptors in brown adipose tissue (BAT) of genetically obese Zucker rats (fa/fa) were studied with [3H]prazosin and [3H]CGP-12177 respectively. 2. The density of alpha 1-adrenergic receptors in BAT was significantly lower in obese than in lean Zucker rats, both at 2-4 months of age and at 6 weeks of age. The density of beta-adrenergic receptors was identical in BAT of lean and obese 6-week-old Zucker rats. 3. Cold-acclimation increased the alpha 1-receptor density significantly in BAT of both lean and obese Zucker rats, and the number of beta-receptors was also somewhat increased. 4. Sucrose feeding did not affect the density of alpha 1-receptors in BAT of lean or obese Zucker rats, but it increased beta-receptor density. 5. Adrenalectomy restored the density of alpha 1-adrenergic receptors in BAT of obese Zucker rats to the value observed in lean rats. 6. It is concluded that there is a direct correlation between alpha 1-receptor density and tissue recruitment, and that alpha 1-receptor density is thus positively correlated with sympathetic activity. beta-Receptor density is apparently better correlated with feeding conditions.     

Peak blood ammonia and lactate after submaximal, maximal and supramaximal exercise in sprinters and long-distance runners

The purpose of this study was to elucidate the difference in peak blood ammonia concentration between sprinters and long-distance runners in submaximal, maximal and supramaximal exercise. Five sprinters and six long-distance runners performed cycle ergometer exercise at 50% maximal, 75% maximal, maximal and supramaximal heart rates. Blood ammonia and lactate were measured at 2.5, 5, 7.5, 10 and 12.5 min after each exercise. Peak blood ammonia concentration at an exercise intensity producing 50% maximal heart rate was found to be significantly higher compared to the basal level in sprinters (P less than 0.01) and in long-distance runners (P less than 0.01). The peak blood ammonia concentration of sprinters was greater in supra-maximal exercise than in maximal exercise (P less than 0.05), while there was no significant difference in long-distance runners. The peak blood ammonia content after supramaximal exercise was higher in sprinters compared with long-distance runners (P less than 0.01). There was a significant relationship between peak blood ammonia and lactate after exercise in sprinters and in long-distance runners. These results suggest that peak blood ammonia concentration after supramaximal exercise may be increased by the recruitment of fast-twitch muscle fibres and/or by anaerobic training, and that the processes of blood ammonia and lactate production during exercise may be strongly linked in sprinters and long-distance runners.     

Expression of exercise-induced HSP70 in long-distance runner''s leukocytes

This study was designed to investigate the expression of heat shock protein 70 (HSP70), after acute moderate intensity exercise, in human peripheral blood leukocytes of trained runners and untrained controls. Ten male long-distance trained runners (TR) and untrained sedentary control subjects (SED) ran for 1 h at 70% of heart rate reserve (HRR). Basal HSP70 expression in TR was usually lower than that in SED, but basal HSP70 gene expression in TR was usually higher than that in SED. Although expression rates of exercise-induced HSP70 in both groups were similar, levels of HSP70 in SED were significantly higher than in TR. Significant increases in leukocytes, neutrophils, and lymphocytes after exercise were observed in both groups, but there were some differences between groups. We conclude that 1 h treadmill running at 70% HRR intensity is a sufficient stimulus to leukocytosis, neutrocytosis, lymphocytosis, and HSP70 proteins and gene expression in leukocytes. Adaptation to training was observed in TR.     

Formation of a functional adrenergic input to intraocular cerebellar grafts: ingrowth of inhibitory sympathetic fibers.

The intraocular transplantation technique was used to study the ingrowth of peripheral sympathetic adrenergic nerves from the iris into transplants of fetal rat cerebellum, and the possible function of these nerves. The transplants, grown in oculo for one-half to eight months, were analyzed by fluorescence histochemistry and electrophysiological techniques. Peripheral sympathetic adrenergic fibers from the iris were able to grow into the cerebellar transplants and arborize in a pattern similar to that in situ, appearing in all three cortical layers and the noncortical areas of the transplants. The density of visible nerves without pretreatment and after preincubation in 10(-6) or 10(-5) M alpha-methylnorepinephrine was comparable to mature rat cerebellum. The spontaneous discharge of the Purkinje cells in oculo was inhibited by microiontophoresis of norepinephrine (NE) and amphetamine in sympathetically innervated, as well as sympathectomized transplants denervated by ganglionectomy. The NE response was blocked by the adrenergic beta-receptor blocker MJ-1999. GABA also inhibited the Purkinje cell activity while glutamate accelerated the discharge. Parenteral amphetamine inhibited Purkinje cell activity in sympathetically innervated transplants, but was ineffective in denervated transplants. The Purkinje cell spontaneous activity was inhibited by electrical stimulation of the NE fiber input through the cervical sympathetic trunk. This inhibition could be antagonized by parenteral reserpine or the beta-adrenergic antagonist propranolol. The responses of the Purkinje cells within the transplants to drugs and transmitters mimic those of the adult rat in situ. In view of the fluorescence histochemical evidence for an ingrowth of peripheral sympathetic adrenergic fibers into the cerebellar transplants, and the results of stimulating the sympathetic trunk, it is suggested that peripheral adrenergic fibers may be able to establish functional connections with the Purkinje cells similar to the cerebellar adrenergic synapses normally formed in situ by fibers from the locus coeruleus.     

Pharmacologic tools for assessment of adrenergic nerve activity in human hypertension

Measurement of plasma norepinephrine concentration (plasma NE) has not resolved the role of the adrenergic system in the pathogenesis or maintenance of hypertension. A better picture is gained if plasma NE measurement is combined with the assessment of sympathetic drive and reactivity by the use of specific sympathetic antagonists and agonists. In mild hypertension, the decrease in heart rate and cardiac output after beta-adrenoceptor blockade correlates with the level of plasma NE. In established hypertension, the fall in blood pressure or peripheral vascular resistance after alpha-adrenoceptor blockade is related to plasma NE levels. Similarly, changes in forearm vascular resistance induced by local alpha-adrenoceptor blockage correlates with plasma NE in hypertension. Cardiovascular responsiveness to adrenergic agonists is altered in hypertension. The response to cardiac beta-receptor stimulation decreases during the course of the disease. To the contrary, vascular responses to exogenous NE increase with the progression of the hypertensive disease. Results with total autonomic blockade indicate that in some patients with early or borderline hypertension, increased sympathetic tone is involved in the maintenance of blood pressure. In established hypertension, there is no definite indication of increased sympathetic tone, but the sympathetic nervous system may nevertheless play a prominent role in the maintenance of the blood pressure. A vascular hyperreactivity to adrenergic stimulation is characteristically associated with established hypertension. The nature of this hyperreactivity has not been fully elucidated, but it is very likely that it reflects structural vascular changes in hypertension.     

Sensitivity to catecholamines and histamine in the trained and in the untrained human organism and sensitivity changes during digestion.

Blood pressure and heart rate responses elicited by norepinephrine, epinephrine and histamine were compared before and after duodenal acidification in 27 trained and untrained young healthy men. Before acidification trained subjects showed a lower sensitivity to norepinephrine and histamine and a slightly lower one to epinephrine. In order to explain these phenomena physical training was supposed to affect alpha, respectively beta adrenergic responsivity in a dissimilar manner. This suggestion was confirmed by the isoproterenol studies, too. Duodenal acidification decreased the catecholamine-induced pressor responses. Depressor responses to histamine did not change in the untrained subjects, whereas they increased in the trained group. Thus, during digestion the histamine-induced depressor responses of trained subjects tended to approach that of untrained people.     

Multiple Adrenergic Receptor Subtypes Controlling Cyclic AMP Formation: Comparison of Brain Slices and Primary Neuronal and Glial Cultures

The adrenergic receptor subtypes involved in cyclic AMP responses to norepinephrine (NE) were compared between slices of rat cerebral cortex and primary neuronal and glial cultures from rat brain. In neuronal cultures, NE and the beta-adrenergic receptor agonist isoproterenol (ISO) caused similar increases in cyclic AMP, which were not altered by the alpha-adrenergic receptor antagonist phentolamine. In glial cultures, NE caused a much smaller cyclic AMP response than did ISO, and this difference was reversed by alpha-adrenergic receptor antagonists (phentolamine greater than yohimbine greater than prazosin). alpha 2-Adrenergic receptor agonists partially inhibited the ISO response in glial cultures to a level similar to that observed with NE alone (clonidine = UK 14,304 greater than NE greater than 6-fluoro-NE greater than epinephrine). In slices from cerebral cortex, NE caused a much larger increase in cyclic AMP than did ISO, and this difference was reversed by alpha-adrenergic receptor antagonists with a different order of potency (prazosin greater than phentolamine greater than yohimbine). alpha 1-Adrenergic receptor agonists potentiated the response to ISO to a level similar to that observed with NE alone (epinephrine = NE greater than phenylephrine greater than 6-fluoro-NE greater than methoxamine). In all three tissue preparations, large responses to both alpha 1-receptor activation (increases in inositol phosphate accumulation) and alpha 2-receptor activation (decreases in forskolin-stimulated cyclic AMP accumulation) were observed. These data indicate that all of the major adrenergic receptor subtypes (beta, alpha 1, alpha 2) are present in each tissue preparation.(ABSTRACT TRUNCATED AT 250 WORDS)     

Differential pre- and postsynaptic effects of desipramine on cardiac sympathetic nerve terminals in RHF

Right heart failure (RHF) is characterized by chamber-specific reductions of myocardial norepinephrine (NE) reuptake, beta-receptor density, and profiles of cardiac sympathetic nerve ending neurotransmitters. To study the functional linkage between NE uptake and the pre- and postsynaptic changes, we administered desipramine (225 mg/day), a NE uptake inhibitor, to dogs with RHF produced by tricuspid avulsion and progressive pulmonary constriction or sham-operated dogs for 6 wk. Animals receiving no desipramine were studied as controls. We measured myocardial NE uptake activity using [(3)H]NE, beta-receptor density by [(125)I]iodocyanopindolol, inotropic responses to dobutamine, and noradrenergic terminal neurotransmitter profiles by glyoxylic acid-induced histofluorescence for catecholamines, and immunocytochemical staining for tyrosine hydroxylase and neuropeptide Y. Desipramine decreased myocardial NE uptake activity and had no effect on the resting hemodynamics in both RHF and sham animals but decreased myocardial beta-adrenoceptor density and beta-adrenergic inotropic responses in both ventricles of the RHF animals. However, desipramine treatment prevented the reduction of sympathetic neurotransmitter profiles in the failing heart. Our results indicate that NE uptake inhibition facilitates the reduction of myocardial beta-adrenoceptor density and beta-adrenergic subsensitivity in RHF, probably by increasing interstitial NE concentrations, but protects the cardiac noradrenergic nerve endings from damage, probably via blockade of NE-derived neurotoxic metabolites into the nerve endings.     

Body composition and isokinetic strength of professional Sumo wrestlers

The purpose of this study was to investigate the profiles of body composition and force generation capability in professional Sumo wrestlers. The subjects were 23 professional Sumo wrestlers [mean age 22.0 (SEM 1.2) years] including those ranked in the lower- (Jonokuchi, n = 10), middle- (Sandanme, n = 8) and higher-division (Makuuchi, n = 5), 22 weight-classified athletes [5 judo athletes, 5 wrestlers, and 12 weight lifters, mean age 20.7 (SEM 0.7) years], and 21 untrained men [mean age 20.1 (SEM 0.2) years]. In the Sumo wrestlers, body mass ranged between 77.0 and 150.0 kg, body mass index between 25.9 and 44.5 kg · m⁻², relative fat mass (%FM) between 11.9 and 37.0%, and fat-free mass (FFM) between 59.1 and 107.6 kg. The Sumo wrestlers showed significantly higher %FM and smaller elbow and knee extensor cross-sectional areas (CSA) than the weight-classified athletes who weighed from 90.4 kg to 133.2 kg. Moreover, isokinetic forces in the flexion and extension of elbow and knee joints, respectively, at three constant velocities of 1.05, 3.14 and 5.24 rad · s⁻¹ were significantly lower in the Sumo wrestlers than in the weight-classified athletes and untrained subjects when expressed per unit of body mass. However, the median value of FFM relative to body height in the higher-division Sumo wrestlers was ranked high in the range of magnitude among those reported previously in the literature for heavyweight athletes. Moreover, the results on the comparisons within the Sumo wrestlers showed that not only FFM but also force generation capability, expressed both as an absolute term and as a value relative to both body mass and muscle CSA, might be factors contributing to the performance of Sumo wrestlers. Accepted: 18 August 1997     

The effect of maximal exercise on the activity of neutrophil granulocytes in highly trained athletes in a moderate training period

Leucocyte cell counts and the phagocytic and chemotactic activities of neutrophil granulocytes were investigated in highly endurance-trained long-distance runners (n = 10) and triathletes (n = 10) during a moderate training period and compared with untrained subjects (n = 10) before and up to 24 h after a graded exercise to exhaustion on a treadmill. After exercise a leucocytosis was noted with a significant increase in lymphocyte (P < or = 0.01) and neutrophil (P < or = 0.01) counts in all groups. In neutrophils the number of ingested inert latex beads was significantly increased (P < or = 0.01) from 0.21 (SD 0.09) to 0.45 (SD 0.22) in controls, from 0.20 (SD 0.12) to 0.56 (SD 0.16) in long-distance runners and from 0.25 (SD 0.08) to 1.03 (SD 0.42) particles per cell in triathletes 24 h after exercise, compared with resting values. The capability of neutrophils to produce microbicidal reactive oxygen species fell (P < or = 0.05) immediately after exercise in all subjects and then increased by 36 (SD 8)%, 31 (SD 6)% and 19 (SD 9)% in controls, runners and triathletes respectively up to 24 h after exercise (P < or = 0.05) compared with pre-start values. With respect to the absolute number of neutrophils, ingestion capacity, production of superoxide anions and chemotactic activity, no significant differences were found between athletes and control subjects at rest and after exercise.(ABSTRACT TRUNCATED AT 250 WORDS)     

Differential alterations in cardiac adrenergic signaling in chronic hypoxia or norepinephrine infusion

Norepinephrine (NE)-induced desensitization of the adrenergic receptor pathway may mimic the effects of hypoxia on cardiac adrenoceptors. The mechanisms involved in this desensitization were evaluated in male Wistar rats kept in a hypobaric chamber (380 Torr) and in rats infused with NE (0.3 mg. kg(-1). h(-1)) for 21 days. Because NE treatment resulted in left ventricular (LV) hypertrophy, whereas hypoxia resulted in right (RV) hypertrophy, the selective hypertrophic response of hypoxia and NE was also evaluated. In hypoxia, alpha(1)-adrenergic receptors (AR) density increased by 35%, only in the LV. In NE, alpha(1)-AR density decreased by 43% in the RV. Both hypoxia and NE decreased beta-AR density. No difference was found in receptor apparent affinity. Stimulated maximal activity of adenylate cyclase decreased in both ventricles with hypoxia (LV, 41%; RV, 36%) but only in LV with NE infusion (42%). The functional activities of G(i) and G(s) proteins in cardiac membranes were assessed by incubation with pertussis toxin (PT) and cholera toxin (CT). PT had an important effect in abolishing the decrease in isoproterenol-induced stimulation of adenylate cyclase in hypoxia; however, pretreatment of the NE ventricle cells with PT failed to restore this stimulation. Although CT attenuates the basal activity of adenylate cyclase in the RV and the isoproterenol-stimulated activity in the LV, pretreatment of NE or hypoxic cardiac membranes with CT has a less clear effect on the adenylate cyclase pathway. The present study has demonstrated that 1) NE does not mimic the effects of hypoxia at the cellular level, i.e., hypoxia has specific effects on cardiac adrenergic signaling, and 2) changes in alpha- and beta-adrenergic pathways are chamber specific and may depend on the type of stimulation (hypoxia or adrenergic).     

Low temperature prevents potentiation of norepinephrine release by phenylephrine

The effect of 1-phenylephrine (1-PE), an alpha(1)-receptor agonist, was investigated on the release of tritiated norepinephrine ([3H]NE). Pairs of guinea pig vasa deferentia were loaded with [3H]NE, superfused continuously, and stimulated electrically. 1-PE (10, 100 microM) enhanced the basal release of tritium in concentration-dependent manner. The stimulation-evoked release of radioactivity was significantly increased by 100 microM 1-PE. Both basal and stimulation-evoked release by 1-PE were reduced by desipramine (10 microM), a monoamine uptake inhibitor. The effect of 1-PE on basal release was independent on extracellular Ca(2+) concentration ([Ca(2+)](o)) and alpha(1)-adrenoceptor blockade. However, the 1-PE-induced release was temperature dependent: at low temperature 1-PE failed to increase either basal or stimulation-evoked release of NE. Using three different temperatures (7, 12, 17 degrees C, respectively), it was found that basal release was blocked at all three temperature values but the stimulation-evoked release was inhibited only at the lower values. The effect of 1-PE on the NE release appears to involve a desipramine-, and temperature-sensitive process. These results suggest that a non-receptorial and direct carrier-mediated mechanism is involved in NE releasing effect of 1-PE.