Postsynaptic Alpha 2-adrenergic Receptors Research Articles

Evaluation of Vascular Pulse Contour Indices over the Physiological Blood Pressure Ranges in an Anesthetized Porcine Model.

A series of physiological measures can be assessed from the arterial pulse waveform, which is beneficial for cardiovascular health diagnosis, monitoring, and decision making. In this work, we have investigated the variations in regional pulse wave velocity (PWVR) and other pulse waveform indexes such as reflected wave transit time (RWTT), augmentation index (Alx), ejection duration index (ED), and subendocardial viability ratio (SEVR) with blood pressure (BP) parameters and heartrate on a vasoconstrictor drug-induced porcine model. Two healthy female (nulliparous and non-pregnant) Sus scrofa swine (~ 80 kg) was used for the experimental study. The measurement system consists of a catheter-based system with two highly accurate pressure catheters placed via the sheath at the femoral and carotid artery for acquiring and recording the pressure waveforms. The pulse waveform indexes were extracted from these recorded waveforms. Results from the pulse contour analysis of these waveforms demonstrated that Phenylephrine, as a post-synaptic alpha-adrenergic receptor agonist that causes vasoconstriction, produced a significant increment in the carotid BP parameters and heartrate. Due to the drug's effect, the PWVR and SEVR were significantly increased, whereas the RWTT, AIx index and ED index significantly decreased.Clinical Relevance- This experimental study provides the usefulness of the pulse contour analysis and estimation of various pulse waveform indexes for cardiovascular health screening and diagnosis.

Dexmedetomidine attenuates the increase of ultrasonographic optic nerve sheath diameter as a surrogate for intracranial pressure in patients undergoing robot-assisted laparoscopic prostatectomy

Background:Pneumoperitoneum and steep Trendelenburg position during robot-assisted laparoscopic prostatectomy (RALP) can increase intracranial pressure (ICP). Dexmedetomidine, a highly selective alpha-2 adrenergic receptor agonist, can cause cerebral vasoconstriction and decrease cerebral blood flow by stimulating the postsynaptic alpha-2 adrenergic receptors on cerebral blood vessels. However, the effects of dexmedetomidine on ICP are controversial and have not been evaluated during RALP under the establishment of pneumoperitoneum in the steep Trendelenburg position. Therefore, we evaluated the effect of dexmedetomidine on optic nerve sheath diameter (ONSD) as a surrogate for assessing ICP during RALP.Methods:Patients were randomly allocated to receive dexmedetomidine (n = 63) (loading dose, 1 μg/kg for 10 minutes and continuous infusion, 0.4 μg/kg/hr) or normal saline (n = 63). The ONSD was measured at 10 minutes after induction of anesthesia in the supine position (T1), 30 minutes (T2) and 60 minutes (T3) after establishment of pneumoperitoneum in the steep Trendelenburg position, and at closing the skin in the supine position (T4). Hemodynamic and respiratory variables were measured at every time point.Results:ONSDs at T2, T3, and T4 were significantly smaller in the dexmedetomidine group than in the control group (5.26 ± 0.25 mm vs 5.71 ± 0.26 mm, 5.29 ± 0.24 mm vs 5.81 ± 0.23 mm, and 4.97 ± 0.24 mm vs 5.15 ± 0.28 mm, all P <.001). ONSDs at T2, T3, and T4 were significantly increased compared to T1 in both groups. Hemodynamic and respiratory variables, except heart rate, did not significantly differ between the 2 groups. The bradycardia and atropine administration were not significantly different between the 2 groups.Conclusion:Dexmedetomidine attenuates the increase of ONSD during RALP, suggesting that intraoperative dexmedetomidine administration may effectively attenuate the ICP increase during pneumoperitoneum in the Trendelenburg position.

Experimental diabetic diarrhea in rats. Intestinal mucosal denervation hypersensitivity and treatment with clonidine.

Diarrhea in streptozocin-induced chronically diabetic rats is caused by an impaired adrenergic regulation of intestinal fluid and electrolyte transport. Stimulation of alpha 2-adrenergic receptors on enterocytes normally promotes NaCl absorption and inhibits HCO3 secretion. The purpose of this study was to determine if adrenergic denervation of intestinal mucosa in chronically diabetic rats alters postsynaptic receptor response, and if the alpha 2-adrenergic agonist clonidine could correct observed fluid malabsorption. Mucosal norepinephrine stores, a measure of adrenergic tone, were markedly reduced in diabetic rats compared with nondiabetic littermates. In vitro, short-circuit current changes to exogenously added l-epinephrine were significantly greater in diabetics, suggesting that denervation hypersensitivity was due to increased numbers of postsynaptic alpha 2-adrenergic receptors. In vivo loop studies demonstrated net fluid secretion in the ileum and colon of diabetics. In diabetics, clonidine reversed the secretion to absorption, but it had no effect on fluid absorption in controls. We conclude that diabetic diarrhea in streptozocin-induced chronically diabetic rats is due to impaired adrenergic regulation of mucosal ion transport, accompanied by a postsynaptic denervation hypersensitivity that can be reversed by clonidine, and accompanied by net intestinal fluid secretion that can be effectively reversed with clonidine.

Chromatophores and color revelation in the blue variant of the Siamese fighting fish ( Betta splendens)

Our light and electron microscopy observations have revealed that the chromatic unit for the caudal fin in the blue variant of the Siamese fighting fish consists exclusively of dermal chromatophores comprised of compact and overlapping light-reflecting motile iridophores underlined by a layer of light absorbing melanophores. The 2 subtypes that make up about 70% of the skin tissue are located just below the basal layer of the considerably thin epidermis. The administration of K-rich saline or norepinephrine induced prompt, but gradual and reversible, changes in the color of the skin from blue to a brown-yellowish color. The induced color change is attributable either to the neurotransmitter releasing effects of the K-rich saline or to the direct effects of norepinephrine on the postsynaptic alpha adrenergic receptors. Both of these agents induced aggregation of the melanosomes within the melanophores and apparently shifted the wavelength of the light reflected by the iridophores towards the shorter (blue) end of the spectrum. Based on the distribution and architectural arrangement of the iridophores and melanophores as well as their physiological responses, we conclude that the generation of the blue coloration in this fish predominantly occurs through motile iridophores via a multilayered thin-film interference phenomenon of the non-ideal type. The presence of the underlying melanophores provides a black sheet of melanin that enhances the chroma and purity of the color.

Postsynaptic α-2 Adrenergic Receptors are Critical for the Antidepressant-Like Effects of Desipramine on Behavior

The antidepressant desipramine inhibits the reuptake of norepinephrine (NE), leading to activation of both pre- and postsynaptic adrenergic receptors, including alpha-1, alpha-2, beta-1, and beta-2 subtypes. However, it is not clear which adrenergic receptors are involved in mediating its antidepressant effects. Treatment of mice with desipramine (20 mg/kg, i.p.) produced an antidepressant-like effect, as evidenced by decreased immobility in the forced-swim test; this was antagonized by pretreatment with the alpha-2 adrenergic antagonist idazoxan (0.1-2.5 mg/kg, i.p.). Similarly, idazoxan, administered peripherally (0.5-2.5 mg/kg, i.p.) or centrally (1-10 microg, i.c.v.), antagonized the antidepressant-like effect of desipramine in rats responding under a differential-reinforcement-of-low-rate (DRL) 72-s schedule, ie, decreased response rate and increased reinforcement rate. By contrast, pretreatment with the beta-adrenergic antagonists propranolol and CGP-12177 or the alpha-1 adrenergic antagonist prazosin did not alter the antidepressant-like effect of desipramine on DRL behavior. The lack of involvement of beta-adrenergic receptors in mediating the behavioral effects of desipramine was confirmed using knockout lines. In the forced-swim test, the desipramine-induced decrease in immobility was not altered in mice deficient in beta-1, beta-2, or both beta-1 and beta-2 adrenergic receptors. In addition, desipramine (3-30 mg/kg) produced an antidepressant-like effect on behavior under a DRL 36-s schedule in mice deficient in both beta-1 and beta-2 adrenergic receptors. As antagonism of presynaptic alpha-2 adrenergic receptors facilitates NE release, which potentiates the effects of desipramine, the present results suggest that postsynaptic alpha-2 adrenergic receptors play an important role in its antidepressant effects.

Nisoxetine infusion into the olfactory bulb enhances the capacity for male rats to identify conspecifics.

In the present report, the norepinephrine uptake inhibitor nisoxetine as well as a cocktail of nisoxetine and the alpha-adrenergic receptor antagonist phentolamine were infused unilaterally into the olfactory bulb during microdialysis to assess their effects upon the capacity of male rats to identify conspecifics. A social discrimination test was conducted while simultaneously measuring olfactory bulb norepinephrine output in the dialysate before, during, and after behavioral testing. Nisoxetine significantly increased norepinephrine levels in the olfactory bulb compared with the Ringer's solution control group. Following such increases in olfactory bulb norepinephrine, identification responses were enhanced compared with that observed in the Ringer's control. In the presence of phentolamine, nisoxetine elevated olfactory bulb norepinephrine to levels similar to that obtained in the nisoxetine alone group, however, investigatory responses directed to the conspecifics indicated an absence of identification capacity similar to that observed in the Ringer's control group. These results reveal a direct link between norepinephrine transmission in the olfactory bulb and enhanced identification via its activation of postsynaptic alpha-adrenergic receptors. These results also show that inhibition of norepinephrine uptake may represent an important mechanism involved with the enhancement of social identification and suggest a possible novel effect for the antidepressant nisoxetine.

Effect of naringin and naringenin on contractions induced by noradrenaline in rat vas deferens—I. Evidence for postsynaptic alpha-2 adrenergic receptor

1. 1. Naringin at all doses (2 × 10 −6, 5 × 10 −7, and 1 × 10 −7 M) significantly increased contractions induced by noradrenaline in rat vas deferens but the increments of maximal contraction were not concentration-dependent. 2. 2. In a medium containing 1 × 10 −6 M yohimbine (a selective blocker of α 2-adrenoceptor) and naringin, the curve constructed with noradrenaline decreased below the control curve. 3. 3. Naringenin (aglycone of naringin) (2 × 10 −6 and 1 × 10 −7 M) increased the contractile effect of noradrenaline and the maximal effect evoked was related to the maximal dose of naringenin. 4. 4. The α 2 antagonism produced by yohimbine in the naringenin-noradrenaline association were retained at two doses of naringenin tested and we noticed a similar behaviour when we used clonidine-noradrenaline.

Participation of alpha 2-adrenergic receptors in neural vascular tone of canine skeletal muscle.

Studies were carried out in anesthetized, paralyzed, and ventilated dogs to determine whether postsynaptic alpha 2-adrenergic receptors participated in neurally mediated vascular tone in skeletal muscle. Hindlimb skeletal muscle resistance (RL) and blood flow (QL) were determined before, during, and after reversible cold block of the sciatic nerve. This sequence of observations was repeated 30 min after blockade of alpha 1-adrenergic receptors with prazosin. Then the alpha 2-adrenergic receptors were blocked with yohimbine, and the nerve cold block was repeated. When the sciatic nerve was cold blocked before alpha 1-adrenergic blockade, RL decreased approximately 50% and QL increased 75% (P less than 0.05) and then returned to control when the nerve was rewarmed. After alpha 1-block 76% of neural tone remained as assessed by nerve cooling (P less than 0.05). This phenomenon occurred despite effective alpha 1-adrenergic blockade as assessed by the alpha 1-receptor agonist methoxamine. With alpha 1- plus alpha 2-block no change in RL or QL was seen with nerve cold block. The same protocol was repeated in a second series of animals, but mean arterial pressure, which fell after alpha 1-block in the group above, was maintained by dextran infusion at normotensive levels. In these animals, 40% of neural tone remained after alpha 1-block. Both alpha 1- and alpha 2-adrenergic blockers were again needed to abolish the QL and RL response to nerve cold block. In another series of animals, yohimbine was administered before prazosin. In this series, alpha 2-adrenergic blockade greatly reduced neural tone as assessed by nerve cooling.(ABSTRACT TRUNCATED AT 250 WORDS)

Endothelin inhibits presynaptic adrenergic neurotransmission in rat mesenteric artery

The effect of endothelin(ET) on adrenergic neurotransmission was examined in isolated perfused rat mesenteric arteries. Porcine ET(10 −12to 10 −10M) attenuated the pressor response to sympathetic nerve stimulation(NS). It also stimulated the release of prostaglandin E 2 (PGE 2), but its inhibition of the pressor response to NS was not affected by indomethacin treatment. ET also caused dose-dependent inhibition of [ 3H]norepinephrine release during NS. Higher doses of ET rather enhanced the pressor response to NS. These results suggest that ET inhibits presynaptic adrenergic neurotransmission without mediation of PGE 2, while it potentiates the responsiveness of the postsynaptic alpha-adrenergic receptor. Thus ET appears to act directly on the neuroeffector junction as well as on the peripheral vasculature.

Role of Postsynaptic α‐Adrenergic Receptors in the β ‐Adrenergic Stimulation of Melatonin Production in the Syrian Hamster Pineal Gland in Organ Culture

The role played by postsynaptic alpha-adrenergic receptors in the stimulation of pineal melatonin production was investigated in the Syrian hamster. The studies were conducted using organ cultured pineal glands collected from both anatomically intact and superior cervical ganglionectomized hamsters. Results obtained indicate that phenylephrine, an alpha-adrenergic agonist, by itself has no effect in promoting melatonin production; however, it potentiates the stimulatory effects of isoproterenol, a beta-adrenergic agonist, on pineal melatonin production in nonoperated hamsters. Similar observations were obtained with pineal glands whose presynaptic terminals were removed by prior superior cervical ganglionectomy. However, a longer incubation time was required (4-6 hours vs. 2 hours) with pineal glands taken from ganglionectomized animals. Apparently, beta-adrenergic activation is an absolute requirement to stimulate pineal melatonin production, and an alpha-adrenergic receptor mechanism potentiates beta-adrenergic activation. In addition, the findings obtained with denervated pineal glands suggest that the regulation of pineal melatonin production by both alpha- and beta-adrenergic mechanisms is through receptors located on postsynaptic structures.

Responsiveness of superficial hand veins to phenylephrine in essential hypertension. Alpha adrenergic blockade during prazosin therapy.

Patients with essential hypertension show an increase in vascular resistance. It is unclear whether this is caused by structural changes in the arterial wall or by hyperresponsiveness of vascular smooth muscle to endogenous alpha adrenergic agonists. Using the dorsal hand vein compliance technique we compared the changes in diameter of superficial veins in response to phenylephrine, an alpha 1 adrenergic receptor agonist, and to nitroglycerin, a venorelaxant, in patients with essential hypertension and in normotensive subjects. The dose of phenylephrine that produced 50% of maximal venoconstriction (ED50) in the hypertensive subjects was 257 ng/min (geometric mean; log mean +/- SD was 2.41 +/- 0.54). In the control subjects the ED50 was 269 ng/min (geometric mean; log mean was 2.43 +/- 0.43). Maximal response (Emax) for phenylephrine was 84 +/- 13% in the hypertensive subjects and 90 +/- 6% in the control subjects. Differences in the group means of the ED50 (P = 0.92) or the Emax (P = 0.27) were not significant. There were no significant differences in the ED50 (P = 0.54) or the Emax (P = 0.08) for nitroglycerin between the two groups. These results show no evidence for a generalized change in alpha adrenergic responsiveness in hypertension and support the concept that increased blood pressure responses to alpha adrenergic stimulation in hypertensives are due to structural and geometric changes in the arterial wall rather than to an increased responsiveness of postsynaptic alpha adrenergic receptors. The phenylephrine studies were repeated in seven hypertensive patients during treatment with prazosin, an alpha 1 adrenergic antagonist. The mean dose ratio of the shift in phenylephrine ED50 (ED50 during prazosin therapy/ED50 before prazosin therapy) was 6.1. This indicates that small doses of prazosin (1-2 mg) cause significant in vivo shifts in the dose-response relationship of alpha adrenergic agonists. The dorsal hand vein compliance technique is useful in detecting systemic effects of alpha adrenergic antagonists.

Presynaptic and postsynaptic alpha 2-adrenergic receptors in human cerebral arteries and their alteration after subarachnoid hemorrhage.

The nature of alpha-adrenergic receptors in human cerebral arteries was characterized, and alteration of these receptors after subarachnoid hemorrhage was examined using a radioligand binding assay. Norepinephrine content of control arteries was also analyzed and compared with that of arteries after subarachnoid hemorrhage. Norepinephrine content in human cerebral arteries in cases of subarachnoid hemorrhage was about 5% of the control group. Specific binding of [3H]yohimbine, a selective alpha 2-antagonist, to cerebral arteries of the control group indicated two classes of binding sites: high-affinity sites with KD of 0.5 nM and Bmax of 18 fmol/mg protein and low-affinity sites with KD of 29 nM and Bmax of 248 fmol/mg protein. In cerebral arteries obtained from the subarachnoid hemorrhage group, [3H]yohimbine binding sites were of a single class with KD of 53 nM and Bmax of 456 fmol/mg protein. These results suggest that sympathetic denervation and subsequent alterations in alpha 2-adrenergic receptors occurred after subarachnoid hemorrhage in human cerebral arteries. These changes in sympathetic innervation to cerebral arteries were considered to be one of the antecedents of delayed vasospasm after subarachnoid hemorrhage.

The differential effects of alpha 2-adrenergic stimulation on the myocardium and coronary vessels in the isolated rat heart.

The differential effects of alpha 2-adrenoceptor stimulation on myocardial contractility and coronary circulation were examined in the isolated perfused rat heart. We studied 20 Sprague-Dawley rats of similar age (26-28 weeks) and body weight (500-550 gm). Myocardial contractility (LV +dp/dt and developed pressure, LVP) and coronary flow resistance (CFR) were tested in the isolated isovolumic hearts using Langendorff preparation at a constant perfusion rate (2.5 ml/min/100 g BW) of Krebs-Henseleit bicarbonate solution. Group I (N-7) received B-HT 920 (specific alpha 2-adrenergic agonist, 0.6 to 58 micrograms/min), Group II (N-7) received B-HT 920+Yohimbine (300 nM in the perfusate). Group III (N-6) received vehicle only. Baseline LVP, LV +dP/dt and CFR were not significantly different among the 3 groups. During drug or vehicle administration, LVP and LV +dP/dt remained unchanged in all the groups. Coronary flow resistance increased in a dose-response fashion with a maximum increase of 22.7 +/- 3.6 (SE) mmHg/ml/min/g LV in Group I, and 10.5 +/- 2.0 mmHg/ml/min/g LV in Group II (p less than 0.02). We conclude that in the Sprague-Dawley rat heart, the physiologic effects of alpha 2-adrenoceptors are predominant in the coronary circulation but not in the myocardium itself possibly because of absence of post-synaptic alpha 2-adrenergic receptors in the rat myocardium.

Interaction between alpha 2- and beta 2-adrenergic receptors in rabbit ciliary processes.

The interaction between the alpha 2- and beta 2-adrenergic receptors of ciliary processes has been studied by examining dose-response curves for adrenergic agonist stimulation of cyclic AMP production by intact, excised rabbit ciliary processes. Stimulation of cyclic AMP production by 1-isoproterenol is maximum from 0.1 to 1.0 microM; at higher concentrations stimulation decreases and approaches basal levels. Decreased cyclic AMP production at high concentrations of isoproterenol is blocked by the specific alpha 2-adrenergic antagonist, yohimbine, but not by the alpha 1-adrenergic antagonist, prazosin. Ciliary processes from animals after bilateral cervical ganglionectomy also show reduced cyclic AMP production at high concentrations of isoproterenol and this reduction is blocked by yohimbine, but not prazosin. This experiment suggests that the inhibition at high concentrations of isoproterenol is mediated by postsynaptic alpha 2-adrenergic receptors. Cyclic AMP production is relatively insensitive to epinephrine and norepinephrine, but their responses are potentiated by yohimbine. Catecholamines and clonidine, a specific alpha 2-adrenergic agonist, exhibit dose-dependent inhibition of forskolin-stimulated cyclic AMP production by ciliary processes. I50s from the dose-response curves are consistent with the characteristic binding affinities of these adrenergic agonists for alpha 2-adrenergic receptors: clonidine = epinephrine greater than norepinephrine greater than isoproterenol. Inhibition of forskolin-stimulated cyclic AMP production by clonidine is blocked by yohimbine but not by prazosin.(ABSTRACT TRUNCATED AT 250 WORDS)

Postsynaptic alpha 1- and alpha 2-adrenergic receptors in adrenergic control of capacitance vessel tone in vivo.

The involvement of postsynaptic alpha 2-adrenergic receptors in the adrenergic constriction of the capacitance vessels was studied in anesthetized, spontaneously breathing dogs under ganglionic blockade (hexamethonium, 10 mg/kg + 10 mg/kg/hr; methylatropine, 0.5 mg/kg). Effective vascular compliance was measured as an indicator of venous tone (blood volume was varied by +/- 4 ml/kg in an 11-minute cycle of infusion, withdrawal, withdrawal, and reinfusion) and was calculated from the correlation between the observed changes in central venous pressure and the changes in blood volume. Sympathetic activity and central venous pressure were lower and effective vascular compliance was higher than values in untreated conscious dogs. The alpha 2-agonist UK 14,304 (5-bromo-6-[imidazolin-2-ylamino]-quinoxaline; 0.04 and 0.12 micrograms/kg/min; n = 6) dose-dependently lowered compliance and increased central venous pressure to levels found in conscious dogs, as did the alpha 1-agonist methoxamine (10 and 30 micrograms/kg; n = 6). Rauwolscine (alpha 2-antagonist), 0.3 mg/kg, significantly attenuated the effects of UK 14,304, but not those of methoxamine, while prazosin (alpha 1-antagonist), 0.12 mg/kg, attenuated the effects of methoxamine, but not those of UK 14,304 (n = 6 each). Under beta-blockade (nadolol, 2 mg/kg; n = 12) venous tone was increased to about physiological levels by norepinephrine, 0.15 micrograms/kg/min i.v., or by neuronal norepinephrine release induced by tyramine, 10 micrograms/kg/min i.v. These increases were significantly attenuated by prazosin as well as by rauwolscine and were abolished by a combination of both. These results indicate that postsynaptic alpha 2-adrenergic receptors (in addition to alpha 1-adrenergic receptors) are functional in the venous system in vivo and contribute substantially to adrenergic sympathetic and humoral regulation of venous tone.

Alpha 2-adrenergic receptor function in depression. The cortisol response to yohimbine.

There is evidence that the abnormalities in hypothalamic-pituitary-adrenal (HPA) axis function observed in patients with depression may be related to changes in central neurotransmitter receptor function. To evaluate this possibility further, the alpha 2-adrenergic receptor antagonist yohimbine hydrochloride, which increases brain norepinephrine turnover, was administered to 40 patients with DSM-III major depression (18 melancholic, 22 nonmelancholic) and 16 healthy controls. Plasma free 3-methoxy-4-hydroxyphenylglycol (MHPG) level was measured as an index of noradrenergic function, and plasma cortisol level was used to assess the HPA response. Baseline cortisol levels were elevated in melancholic depressed patients, but not in nonmelancholic patients, when compared with healthy controls. The cortisol response to yohimbine was significantly greater in depressed patients than in controls, despite similar MHPG responses between groups. Since there is evidence that stimulation of postsynaptic alpha 2-adrenergic receptors inhibits HPA axis function, the abnormally increased cortisol response to the alpha 2-antagonist yohimbine suggests a relative subsensitivity of postsynaptic alpha 2-adrenergic receptors in depression.

A clinical approach for the identification of peripheral pre- and post-synaptic alpha-adrenergic receptors.

The present study examines the possibility that pre- and post-synaptic alpha-adrenergic receptors can be differentiated by a clinical pharmacological approach. We compared the ability of the alpha 1-selective antagonists, prazosin and urapidil, with the ability of the alpha 2-selective antagonist, yohimbine, to inhibit cardiovascular responses to the non-selective alpha-adrenergic agonist norepinephrine in 26 healthy volunteers. Urapidil (50 mg i.v.) and prazosin (5 mg orally) induced significant shifts to the right in the blood pressure dose-response curve of norepinephrine. Yohimbine (10 mg orally), on the other hand, increased norepinephrine sensitivity, as indicated by a significant shift to the left of the norepinephrine dose-response curve. In addition, urapidil and prazosin decreased norepinephrine potency on heart rate, whereas no effect on norepinephrine-induced heart rate elevation was observed with yohimbine. From the studies in which yohimbine was used it can be assumed that the post-synaptic response to norepinephrine is not counteracted by the drug-induced inhibition of sympathetic neurotransmitter release. Hence, our findings confirm the presence of pre- and post-synaptic alpha-adrenergic receptors in man.

A Pharmacological Study of Alpha Adrenergic Receptor Subtypes in Smooth Muscle of Human Urinary Bladder Base and Prostatic Urethra

Postsynaptic alpha adrenergic receptor subtypes mediating contraction of human urinary bladder base and prostatic urethra were investigated in vitro. Alpha adrenergic receptor agonists, noradrenaline and phenylephrine, induced contraction dose-dependently in these tissues. Alpha adrenergic receptor antagonists, prazosin and yohimbine, competitively antagonized the contraction induced by these agonists in the bladder base as well as prostatic urethra. The mean pA2 values for the antagonists in the bladder base and prostatic urethra were as follows: 8.89 and 8.96 for prazosin and 6.30 and 6.45 for yohimbine, respectively. Comparison of pA2 values of prazosin and yohimbine in both the tissues with those values found in the literature for these compounds in a variety of tissues containing alpha-1 or alpha-2 adrenergic receptor indicates that the postsynaptic alpha adrenergic receptor subtype in the human urinary bladder base and prostatic urethra is the alpha-1 type, not the alpha-2 type.

Characteristics of postsynaptic alpha 1 and alpha 2 adrenergic receptors in canine vascular smooth muscle.

A previous study suggested the existence of two distinct postsynaptic alpha adrenergic receptors in canine intralobar pulmonary arteries (IPA) and veins. The present study, performed using rings of canine IPA and dorsal metatarsal vein (DMV), was designed to characterize the factors affecting the postsynaptic alpha 1 and alpha 2 receptors of these blood vessels. The responses of IPA and DMV to norepinephrine (NE), transmural nerve stimulation, phenylephrine (PE), guanabenz, and clonidine were obtained in the presence and absence of alterations in pH, extracellular calcium ion, sulfhydryl bond reduction and oxidation, and destruction of adrenergic nerves with 6-hydroxydopamine. The data demonstrate that: (i) alpha 2-receptors are inactivated by changes in pH above or below pH 7.4, contain a labile disulfide group, are susceptible to modulation by increases and decreases in calcium ion, and appear to be decreased by destruction of adrenergic nerves; (ii) the NE and PE sensitive alpha 1-receptors are insensitive to alterations in pH, refractory to disulfide reduction by dithiothreitol, slightly susceptible to modulation by calcium ion, and increased by destruction of adrenergic nerves. These data support the conclusion that the two subtypes of postsynaptic alpha adrenergic receptors differ in their properties and susceptibility to modification by alteration of the physiological environment.

Clonidine-induced growth hormone secretion in chronic schizophrenia.

Clonidine (0.15 mg intravenously), an alpha-adrenergic receptor agonist, was administered to 13 male chronic schizophrenics, who had been withdrawn from chronic neuroleptic therapy, and to 18 normal male controls. There was no significant difference in growth hormone (GH) response between the two groups. There was no significant correlation between duration of psychosis, duration of neuroleptic therapy or length of neuroleptic withdrawal and GH response. These results suggest that postsynaptic alpha-adrenergic receptor function in the hypothalamic-pituitary axis is unaltered in chronic schizophrenia or by prior chronic neuroleptic therapy.