Relationship between cortical electrical and cardiac autonomic activities in the awake lizard, Gallotia galloti

ECG and EEG signals were simultaneously recorded in lizards, Gallotia galloti, both in control conditions and under autonomic nervous system (ANS) blockade, in order to evaluate possible relationships between the ANS control of heart rate and the integrated central nervous system activity in reptiles. The ANS blockers used were prazosin, propranolol, and atropine. Time-domain summary statistics were derived from the series of consecutive R-R intervals (RRI) of the ECG to measure beat-to-beat heart rate variability (HRV), and spectral analysis techniques were applied to the EEG activity to assess its frequency content. Both prazosin and atropine did not alter the power spectral density (PSD) of the EEG low frequency (LF: 0.5-7.5 Hz) and high frequency (HF: 7.6-30 Hz) bands, whereas propranolol decreased the PSD in these bands. These findings suggest that central beta-adrenergic receptor mechanisms could mediate the reptilian waking EEG activity without taking part any alpha(1)-adrenergic and/or cholinergic receptor systems. In 55% of the lizards in control conditions, and in approximately 43% of the lizards under prazosin and atropine, a negative correlation between the coefficient of variation of the series of RRI value (CV(RRI)) and the mean power frequency (MPF) of the EEG spectra was found, but not under propranolol. Consequently, the lizards' HRV-EEG-activity relationship appears to be independent of alpha(1)-adrenergic and cholinergic receptor systems and mediated by beta-adrenergic receptor mechanisms.     

Selective alpha2-adrenergic properties of dexmedetomidine over clonidine in the human forearm.

We tested the hypothesis that dexmedetomidine (Dex) has greater alpha(2)- vs. alpha(1) selectivity than clonidine and causes more alpha(2)-selective vasoconstriction in the human forearm. After local beta-adrenergic blockade with propranolol, forearm blood flow (plethysmography) responses to brachial artery administration of Dex, clonidine, and phenylephrine (alpha(1)-agonist) were determined in healthy young adults before and after alpha(2)-blockade with yohimbine (n = 10) or alpha(1)-blockade with prazosin (n = 9). Yohimbine had no effect on phenylephrine-mediated vasoconstriction but blunted Dex-mediated vasoconstriction (mean +/- SE: -41 +/- 5 vs. -11 +/- 2%; before vs. after yohimbine) more than clonidine-mediated vasoconstriction (-39 +/- 5 vs. -28 +/- 4%; before vs. after yohimbine) (P < 0.02). Prazosin blunted phenylephrine-mediated vasoconstriction (-39 +/- 4 vs. -8 +/- 2%; before vs. after prazosin) but had similar effects on both Dex- (-30 +/- 4 vs. -39 +/- 6%; before vs. after prazosin) and clonidine-mediated vasoconstriction (-29 +/- 3 vs. -41 +/- 7%; before vs. after prazosin) (P > 0.7). Both Dex and clonidine reduced deep forearm venous norepinephrine concentrations to a similar extent (-59 +/- 12 vs. -55 +/- 10 pg/ml; Dex vs. clonidine, P > 0.6); this effect was abolished by yohimbine and blunted by prazosin. These results suggest that Dex causes more alpha(2)-selective vasoconstriction in the forearm than clonidine. The similar vasoconstrictor responses to both drugs after prazosin might be explained by the presynaptic effects on norepinephrine release.     

Catecholaminergic regulation of the hypothalamic-pituitary-adrenocortical activity.

The significance and site of adrenergic receptors involved in the control of the hypothalamic-pituitary-adrenal axis (HPA) activity was assessed indirectly by estimation of serum corticosterone levels 1 h after drug administration to conscious rats. Adrenergic drugs were given intracerebroventricularly (icv) and intraperitoneally (ip), the antagonists 15 min prior to the agonists. Noradrenaline, adrenalin and isoproterenol given by either route increased dose-dependently the serum corticosterone levels. The corticosterone response to icv noradrenaline was almost abolished by icv pretreatment with propranolol, a beta-adrenergic antagonist, and yohimbine, and alpha 2-receptor blocker, and was also considerably reduced by prazosin, an alpha 1-adrenergic antagonist. When given ip, these antagonists did not significantly influence the noradrenaline induced corticosterone response, which suggests a suprapituitary site of action of noradrenaline in stimulation of the HPA. The corticosterone response to icv adrenalin was suppressed by prazosin given by either route. The corticosterone response to ip adrenalin was almost abolished by pretreatment with yohimbine, and also significantly diminished by propranolol given by the same route. The increase in corticosterone secretion, induced by isoproterenol given by either route, was abolished by ip injection of propranolol. These results indicate that noradrenaline stimulates the HPA via alpha- and beta-adrenergic receptors, mainly at the suprapituitary level. Adrenalin increases that activity both via central and pituitary alpha- and beta-adrenoceptors. Isoproterenol activates the HPA by stimulation of pituitary beta-receptors.     

N-Acetylation of Serotonin Is Correlated with α2- but Not with β-Adrenergic Regulation of Cyclic AMP Levels in Cultured Chick Pineal Cells

We investigated the role of cyclic AMP (cAMP) in alpha 2- and possible beta-adrenergic regulation of arylalkylamine-N-acetyltransferase (NAT), the penultimate enzyme in the biosynthesis of melatonin. The study was performed on primary cultures of dispersed chick pineal cells. Electron microscopy indicated that approximately 70% of the dispersed cells were modified photoreceptors. A similar proportion of melatoninergic cells was detected by immunocytochemical labeling of hydroxyindole-O-methyltransferase, the final enzyme in the biosynthesis of melatonin. Adrenergic agonists caused a sustained 50% inhibition of forskolin-augmented cAMP levels and NAT activity, with an alpha 2-adrenergic potency order of UK 14,304 greater than or equal to clonidine greater than norepinephrine greater than phenylephrine. Noradrenergic inhibition of 3-isobutyl-1-methylxanthine-augmented cAMP levels and NAT activity was reversed by yohimbine (an alpha 2-adrenergic antagonist) but not by prazosin (an alpha 1-adrenergic antagonist). The alpha-adrenergic inhibition of cAMP accumulation and NAT activity was prevented by pertussis toxin. Addition of propranolol (a beta-adrenergic antagonist) was necessary to observe an inhibitory effect of norepinephrine on cAMP levels but not on NAT activity. Similarly, the beta-adrenergic agonist isoproterenol transiently increased cAMP levels but did not affect NAT activity. The data indicate that the alpha 2-adrenergic inhibition of NAT activity in chick pineal cells is strongly correlated with an inhibition of cAMP accumulation. The lack of beta-adrenergic effect on NAT suggests that beta-adrenoceptors might be on a subset of cells that do not produce melatonin or that the beta-adrenergic-induced increase in cAMP levels is too transient to affect NAT.     

Inhibition of the lipolytic action of beta-adrenergic agonists in human adipocytes by alpha-adrenergic agonists

The aim of this study was to define the role of the alpha-adrenergic receptor in the regulation of lipolysis by human adipocytes. Glycerol production by isolated human adipocytes was stimulated by the pure beta-adrenergic agonist isoproterenol in a dose-dependent fashion. This stimulation of lipolysis was inhibited by the alpha-adrenergic agonists methoxamine, phenylephrine, and clonidine. Epinephrine-stimulated lipolysis was potentiated by the alpha-adrenergic antagonists, dihydroergocryptine, phentolamine, phenoxybenzamine, and yohimbine. Whereas the attenuation of beta-adrenergic agonist-stimulated lipolysis by alpha-adrenergic agonists was reversed completely by the alpha 2-adrenergic antagonist yohimbine, the alpha 1-antagonist prazosin did not reverse such attenuation. It is concluded that alpha-adrenergic agonists act as antilipolytic agents in human adipocytes and that this action may result from the interaction of these compounds with a population of alpha 2-adrenergic receptors.     

Detection and sources of nonlinearity in the variability of cardiac R-R intervals and blood pressure in rats

Beat-to-beat R-R interval (RRV) and systolic blood pressure (SPV) variability signals were obtained from unrestrained rats in baseline and under different pharmacological treatments. The origin and extent of the nonlinearity in both signals, as well as their degree of mutual coupling, was estimated using measurements from the correlation integral (CI) and recurrence quantification analysis (RQA). After the respiratory component of baseline signals was removed, the nonlinearity was lower in the RRV and disappeared in the SPV. This also decreased the RRV-SPV coupling. The nonlinearity of RRV was also reduced after atropine, and the nonlinearity of SPV was strengthened after prazosin and N(omega)-monomethyl-L-arginine (L-NMMA). Atropine and prazosin decreased CI measures of both signals, whereas propranolol, phenylephrine, and L-NMMA decreased only those of SPV. RQA indexes of RRV increased after atropine and decreased after propranolol, whereas the reverse occurred for the RRV-SPV coupling. These results suggest that: 1) the nonlinearity of RRV appears to be very dependent on the parasympathetic activity, whereas that of SPV seems to come from its respiratory component through a nonneural pathway; 2) respiratory component appears to be involved, through the parasympathetic system, in the RRV-SPV coupling; and 3) CI and RQA measures seems to be useful in assessing autonomic mediation of RRV and RRV-SPV coupling.     

Effect of alpha-adrenergic blocking agents on uterine activity in the ewe at the end of gestation

The electromyographic activity (EMG) of the uterus was recorded in vivo in 8 unanaesthetized ewes from the 140th day of gestation up to parturition. The effects on uterine activity of treatments with an alpha 1-receptor blocker (prazosin) and an alpha 2-receptor blocker (yohimbine) were studied. During the last days of gestation, EMG activity consisted of periodic active phases (1-2/h). During the last 16-17 hours, uterine activity increased sharply; this period was referred to a labour. Intravenous perfusion of prazosin (0.03 mg/kg/mn over 1 h) or intravenous injections (1 mg/kg) did not modify uterine activity either before or during labour. Intravenous perfusion of yohimbine (0.03 mg/kg/mn during 1h) inhibited uterine activity before and during labour. In all cases, lambing occurred between the 142nd and 145th day of gestation, which corresponds to the normal lambing period. These results suggest that, in the ewe, uterine alpha 2-receptors are important for normal uterine activity at the end of gestation and in. parturition.     

Interaction of amiloride with alpha-adrenoreceptors: evidence from radioligand binding studies

We investigated the effect of amiloride on alpha-adrenoreceptors (alpha 1 and alpha 2) using radioligand binding techniques. Amiloride inhibited [3H]yohimbine and [3H]prazosin binding to alpha 2- and alpha 1-adrenoreceptors, respectively, from various tissues in a concentration-dependent manner. Amiloride was approximately 9-12 times more potent in inhibiting [3H]yohimbine binding to alpha 2-adrenoreceptors from rat tissues than from other mammalian tissues. However, it had almost the same potency in inhibiting [3H]prazosin binding to alpha 1-adrenoreceptors from rat as well as other mammalian tissues. Further, in rat tissues, amiloride was approximately 10 times more potent in inhibiting [3H]yohimbine than [3H]prazosin binding. Amiloride inhibited [3H]yohimbine binding noncompetitively and [3H]prazosin binding competitively. The inhibition of [3H]yohimbine and [3H]prazosin binding by amiloride was reversible. Since amiloride has been shown to be an inhibitor of Na+-H+ exchanger protein, we believe that it regulates the alpha 2-adrenoreceptors by binding to Na+ -H+ exchanger protein. Triamterene, a compound similar to amiloride in regard to diuretic effect, had very little effect on [3H]yohimbine and [3H]prazosin binding to rat kidney membranes, suggesting that the alpha-adrenoreceptor antagonistic properties of amiloride are not related to its antikaliuretic effect. The results of the present study suggest that some of the pharmacological actions of amiloride (antihypertensive and diuretic effects) can be explained in part by its regulatory effect on both alpha 1- and alpha 2-adrenoreceptors.     

Effect of gamma-aminobutyric acid on corticosterone secretion: involvement of the noradrenergic system.

The administration of gamma-aminobutyric acid (GABA) in the brain right lateral ventricle reduces serum corticosterone levels, and induces significant variations of hypothalamus biogenic amines in conscious male rats. After pretreatment with either alpha 1-adrenergic (prazosin) or alpha 2-adrenergic (yohimbine) blocking agents, the inhibitory effect of GABA on ACTH secretion was prevented. However, we observed that pretreatment with a beta-adrenergic blocking agent (propranolol), did not preventing the inhibitory effect of GABA on serum corticosterone levels. These results indicate that GABA has an inhibitory effect on ACTH secretion mediated by the activation of alpha 1 and alpha 2-adrenergic receptors.     

Interaction of alpha adrenergic antagonists with calmodulin

Several alpha-adrenergic antagonists inhibited the activation of calmodulin-stimulated phosphodiesterase at concentrations that had little or no effect on basal phosphodiesterase activity. The most potent of these compounds were phenoxybenzamine and dibenamine (IC50 values of about 1 microM); the amino acid ergot alkaloids ergocryptine, ergocristine, ergotamine and their dihydrogenated derivatives were less potent calmodulin-inhibitors (IC50 values of 35-80 microM). The amino ergot alkaloids ergonovine and methysergide were essentially devoid of inhibitory activity. A variety of other alpha 1-antagonists (phentolamine, tolazoline and prazosin), an alpha 2-antagonist (yohimbine), alpha-agonists (norepinephrine, phenylephrine and clonidine), beta-adrenergic antagonists (propranolol and practolol) and the beta-adrenergic agonist methoxyphenamine displayed little or no anti-calmodulin activity (IC50 values greater than 300 microM). Similarly, the alkylating agents chlorambucil and mechlorethamine also failed to inhibit calmodulin activity. Phenoxybenzamine and dibenamine inhibited calmodulin activity irreversibly, whereas the inhibition caused by other alpha adrenergic blocking agents was reversible. Phenoxybenzamine inhibited calmodulin activity by binding directly to it. This binding was calcium-dependent and irreversible. The irreversible binding and inhibition of calmodulin activity by phenoxybenzamine (or dibenamine) may serve as a useful tool for studying the sites at which drugs bind to calmodulin and may also be useful for studying the distribution and turnover of calmodulin.     

Synergistic Action of Postsynaptic α-Adrenergic Receptor Stimulation on Vasoactive Intestinal Polypeptide-Induced Increases in Pineal N-Acetyltransferase Activity

The alpha-adrenergic agonists phenylephrine and methoxamine, at concentrations that have little effect on pineal N-acetyltransferase activity, markedly enhance stimulation of this enzyme by vasoactive intestinal polypeptide (VIP). This augmentation can be blocked by the alpha 1-adrenergic antagonists phenoxybenzamine and prazosin and, at 10 but not 1 microM, by the alpha 2-antagonist yohimbine. The time course for VIP stimulation is not altered by concomitant alpha-adrenergic stimulation. Augmented activity does not require concomitant alpha-adrenergic stimulation, but alpha-adrenergic agonists must be present for augmentation to be maintained. Phorbol 12,13-diacetate or -dibutyrate but not 4 alpha-phorbol can substitute for phenylephrine, a finding suggesting that protein kinase C is involved in the augmentation. These results are, in general, analogous to alpha-adrenergic magnification of N-acetyltransferase induction by beta-adrenergic agonists.     

Evaluation of isomers of octopamine for in vitro alpha-adrenergic stimulation of the aortic smooth muscle from spontaneously hypertensive rats

Isomers of octopamine were tested for in vitro alpha-adrenergic stimulation of aortic smooth muscle of spontaneously hypertensive rats (SHR). In order to test the response of alpha 1-adrenoceptors to meta-, para-, and ortho-octopamine, alpha 2-adrenoceptors were blocked with 10(-7) M yohimbine, and to measure the response of alpha 2-adrenoceptors the alpha 1-adrenoceptors were blocked with 10(-7) M prazosin. The contractile response of aortic smooth muscle of SHR to stimulation by phenylephrine, m-, p-, and o-isomers of octopamine in the presence of yohimbine was not appreciably altered. However, administration of prazosin severely attenuated the response of muscles of these compounds indicating that like phenylephrine, the isomers of octopamine stimulate mainly alpha 1-adrenoceptors. The attenuation of contractile response to isomers of octopamine in the presence of prazosin was not as pronounced as in the case of phenylephrine. The comparative potencies of phenylephrine, m-, p-, and o-octopamine in the presence of 10(-7) M prazosin were 1:1.2:2.5:0.75, respectively. Thus, it appears that the isomers of octopamine, especially para- and meta-octopamine, play a much more important role in the physiology of vascular smooth muscle than has been thus far perceived.     

Pharmacological characterization of alpha1- and beta-adrenergic synergism of 5'DII activity in rat brown adipocytes

The role of adrenoceptor subtypes was studied in rat brown adipose tissue (BAT). The type II 5'-deiodinase (5'DII) was activated in response to simultaneous stimulation by beta3- and alpha1-adrenergic agonists, BRL 37344 or CGP 12177, and cirazoline, in brown adipocytes. Inhibition of the alpha1- and beta-adrenergic phenylephrine-stimulated 5'DII activity was obtained by the alpha1-adrenergic antagonists in the order of prazosin >/= wb 4101 > 5-methylurapidil. In comparison, the binding of [3H]prazosin to rat BAT plasma membranes was inhibited by alpha1-adrenergic antagonists in the order of prazosin > WB 4101 = benoxathian > 5-methylurapidil. Although the order of the alpha1-adrenergic competition seemed to be rather typical for the alpha1B-adrenergic receptors, a molecular analysis on adrenoceptor mRNAs should be made to confirm the exact alpha1-adrenergic subtypes at the level of brown adipocytes, since the possibility of a mixture of different receptor subtypes in brown fat cells and/or tissue may interact with the pharmacological characterization. Thus, specific alpha1- and beta-adrenoceptor subtypes participate in the regulation of 5'DII activity in the rat brown adipocytes, and therefore, an impaired alpha1- and beta-adrenergic co-work may be involved in a defective BAT function, e.g., in obese Zucker rats, too. An interesting possibility is that the decreased number of alpha1-adrenoceptors in the BAT of obese Zucker rats is due to the decrease in the alpha1B-adrenoceptor subtype which would further be involved especially in the regulation of BAT 5'DII activity.     

Identification of alpha adrenoceptor subtypes in dog arteries by (3H) yohimbine and (3H) prazosin

Binding of the alpha adrenergic antagonists (³H) prazosin and (³H) yohimbine to membranes of dog arteries exhibit the characteristics expected of alpha adrenoceptors. Binding of both ligands is saturable with dissociation constants of 0.19nM and 1.15nM for (³H) prazosin and (³H) yohimbine respectively. A series of catecholamines inhibit binding of both ligands with a potency in the order $\text{epinephrine}\text{>}\text{norepinephrine}\text{a}\text{?}\text{isoproterenol}$, corresponding with the activity of these agents at alpha adrenoceptors in blood vessels. Competition for binding in both instances is stereoselective. ?-Phenylephrine has similar potencies in inhibiting (³H) prazosin and (³H) yohimbine specific binding whilst the imidazoline related partial alpha adrenergic agonists clonidine and guanfacine are more potent in inhibiting (³H) yohimbine specific binding. The affinity of prazosin for the (³H) yohimbine binding site is approximately 2500 times less than for the (³H) prazosin site whilst yohimbine is approximately 150 times more potent in inhibiting (³H) yohimbine than (³H) prazosin specific binding. Non-selective alpha adrenergic antagonists have similar affinities for both binding sites. The concentrations of (³H) yohimbine binding sites in different arteries vary about two fold whilst for (³H) prazosin the variation was about three fold. These results indicate that there are two discrete noradrenergic binding sites in the major arteries of dog which have binding properties expected of alpha₁ and alpha₂ adrenoceptors.     

Role of autonomic nervous system in the time-dependent hyperglycemia induced by intracranial injection of D-mannitol and D-glucose

Intracranial injection of D-mannitol (MA) or D-glucose (GL) caused photoperiodic hyperglycemia in rats; MA injection elicited hyperglycemia only in the light period, while GL injection induced it only in the dark period. To elucidate the mechanisms of these hyperglycemias, we examined the effect of the autonomic nervous system on them in rats under the L:D (12:12) condition. Propranolol, a beta-adrenergic blocker, and hexamethonium, a ganglion blocker, effectively inhibited hyperglycemia induced in either the light (MA) or dark (GL) period. In contrast, phenoxybenzamine, an alpha-adrenergic blocker, and atropine, a cholinergic blocker, inhibited hyperglycemia induced in the light period (MA), but not that induced in the dark period (GL). These findings suggest that alpha and beta-adrenergic and cholinergic mechanisms are involved in the hyperglycemia induced by MA in the light period, while only the beta-adrenergic mechanism is involved in the hyperglycemia induced by GL in the dark period.     

Down syndrome’s brain dynamics: analysis of fractality in resting state

To the best knowledge of the authors there is no study on nonlinear brain dynamics of down syndrome (DS) patients, whereas brain is a highly complex and nonlinear system. In this study, fractal dimension of EEG, as a key characteristic of brain dynamics, showing irregularity and complexity of brain dynamics, was used for evaluation of the dynamical changes in the DS brain. The results showed higher fractality of the DS brain in almost all regions compared to the normal brain, which indicates less centrality and higher irregular or random functioning of the DS brain regions. Also, laterality analysis of the frontal lobe showed that the normal brain had a right frontal laterality of complexity whereas the DS brain had an inverse pattern (left frontal laterality). Furthermore, the high accuracy of 95.8 % obtained by enhanced probabilistic neural network classifier showed the potential of nonlinear dynamic analysis of the brain for diagnosis of DS patients. Moreover, the results showed that the higher EEG fractality in DS is associated with the higher fractality in the low frequencies (delta and theta), in broad regions of the brain, and the high frequencies (beta and gamma), majorly in the frontal regions.     

Effect of adrenoblockers on the analgesic effect of GABA-positive preparations

The experiments on rats have shown that selective alpha 1 and alpha 2 adrenoceptor blockers (prazosin and yohimbine) and an inhibitor of dopamine-beta-hydrolase FD-008 failed to change the antinociceptive effect of baclofen, a direct GABAB receptor agonist. The antinociceptive effect of THIP and depakin, acting predominantly on GABAA receptors, was significantly reduced by prazosin, FD-008 and yohimbine in vocalization test. In tail-flick test the analgetic effect of THIP and depakin was not altered by prazosin and FD-008, but was increased by yohimbine. The role of adrenergic mechanisms in GABAA and GABAB receptor-mediated analgesia is discussed.     

Biochemical characterization of alpha-adrenergic receptors in human brain and changes in Alzheimer-type dementia

Using ligand binding techniques, we studied alpha-adrenergic receptors in brains obtained at autopsy from seven histologically normal controls and seven patients with histopathologically verified Alzheimer-type dementia (ATD). Binding of the alpha-adrenergic antagonists [3H]prazosin and [3H]yohimbine to membranes of human brains exhibited characteristics compatible with alpha 1- and alpha 2-adrenergic receptors, respectively. Binding of both ligands was saturable and reversible, with dissociation constants of 0.15 nM for [3H]prazosin and 5.5 nM for [3H]yohimbine. [3H]Prazosin binding was highest in the hippocampus and frontal cortex and lowest in the caudate and putamen in the control brains. [3H]Yohimbine binding was highest in the nucleus basalis of Meynert (NbM) and frontal cortex and lowest in the caudate and cerebellar hemisphere in the control brains. Compared with values for the controls, [3H]prazosin binding sites were significantly reduced in number in the hippocampus and cerebellar hemisphere, and [3H]yohimbine binding sites were significantly reduced in number in the NbM in the ATD brains. These results suggest that alpha 1- and alpha 2-adrenergic receptors are present in the human brain and that there are significant changes in numbers of both receptors in selected regions in patients with ATD.     

Ontogeny of alpha 1- and beta-adrenergic receptors in rat lung

The binding characteristics of the alpha 1-selective adrenergic ligand [3H]-prazosin were determined in particulate membranes of rat lung from day 18 of gestation to adulthood. Specific binding was present at all ages studied, was reversible and inhibition of specific binding by agonists followed the order of potency: (-)-epinephrine = (-)-norepinephrine much greater than (-)-isoproterenol greater than (+)-norepinephrine. Inhibition by antagonists followed the order of potency: prazosin greater than WB4101, much greater than yohimbine. Binding capacity increased during the neonatal period from 52 +/- 9 fmoles x mg-1 protein in lung preparations on day 18 of a 21 day gestation increasing to 105 +/- 4 fmoles x mg-1 protein (mean +/- SE) by postnatal day 15. Binding activity decreased thereafter, reaching adult levels by 28 days of postnatal age, 62 +/- 3 fmoles x mg-1 protein. This pattern of alpha 1-adrenergic receptor density was distinct from that of beta-adrenergic receptors identified in rat lung membrane with the beta- adrenergic antagonist, (-)-[3H]dihydroalprenolol ((-)-[3H]DHA). (-)-[3H]DHA binding increased dramatically during this same time period, from 46 +/- 4 fmoles x mg-1 protein on day 18 of gestation to 496 +/- 44 fmoles x mg-1 protein in the adult lung. Affinity for [3H]-prazosin and (-)-[3H]DHA did not change with age. Pulmonary alpha 1-adrenergic receptors are present as early as 18 days of gestation in the rat and alpha 1-adrenergic receptor density is maximal by 15 days of postnatal age. The timing of the changes in alpha 1-adrenergic receptors correlates with the timing of increased sympathetic innervation of the developing rat lung and is distinct from that of beta-adrenergic receptor sites.     

Age-related variation of EEG responses to clonidine, prazosin and yohimbine in rats

The EEG-effects induced by intraperitoneal administration of clonidine, prazosin and yohimbine to 8 and 22 month old rats were compared. Clonidine (0.01 mg/kg) and prazosin (1 mg/kg) increased spectral powers, yohimbine (0.5 mg/kg) decreased them. In the older rats, EEG variations were smaller for prazosin and yohimbine, but larger for clonidine. These findings show that alpha receptor mediated influences on EEG are changed during aging and show that quantified EEG gives a picture of age related changes in the functional state of the neurotransmitter systems.