Effect of adrenergic antagonists during phenylephrine stimulation of the mandibular gland of red kangaroos,Macropus rufus

Intracarotid infusions of l-phenylephrine at 1.0 nmol.kg(-1).min(-1) or(.)10 nmol.kg(-1).min(-1) were accompanied by increases in salivary protein, urea, magnesium and bicarbonate, and by decreases in osmolality, hydrogen ion activity, sodium, potassium and chloride relative to cholinergically stimulated saliva. Intravenous infusions of phenylephrine at the same dose rates had much less effect on salivary composition with the differences between the routes of administration being greatest for the higher dose rate. Propranolol administered with phenylephrine via the carotid artery, at an antagonist:agonist ratio of 10:1, was much more effective in blocking the phenylephrine-induced changes in salivary composition than equimolar infusion of phentolamine with phenylephrine. Simultaneous intracarotid infusions of either a beta(1)-antagonist (CGP20712A) or a beta(2)-antagonist (ICI118551) with phenylephrine showed that ICI118551 was more potent than CGP20712A at preventing the changes in salivary composition associated with phenylephrine administration. It was concluded that alpha(1)-adrenoreceptors were not present in functionally significant numbers in the gland and that the effect of phenylephrine on the kangaroo mandibular was mediated by beta-adrenoreceptors predominantly of the beta(2)-subtype. As the phenylephrine dose rates in the kangaroos were comparable with those used to determine alpha-adrenergic responses of eutherian salivary glands and as both propranolol and phentolamine appeared to have minor beta-sympathomimetic activity, at least one subtype of beta-adrenoreceptors in macropods may not be identical to its eutherian counterpart.     

Salivary secretion during selective β-adrenoreceptor stimulation and blockade in the parotid gland of red kangaroos,<Emphasis Type="Italic"> Macropus rufus</Emphasis>

Intracarotid infusions of noradrenaline (0.3 nmol.kg(-1) x min(-1)) stimulated salivary fluid secretion and caused increases in salivary concentrations of protein, potassium. magnesium. chloride and phosphate, and decreases in bicarbonate. These effects of intracarotid noradrenaline were not reduced by simultaneous intracarotid infusion of phentolamine (3.0 nmol.kg(-1) x min(-1)) but were significantly greater than the responses accompanying intravenous noradrenaline infusion. Concomitant administration of the beta-antagonist, CGP20712A, were much more effective in blocking the noradrenaline-induced changes in salivary composition than equimolar infusions of the beta2-antagonist, ICI118551, thereby confirming the presence of beta1-adrenoreceptors. Intracarotid infusion of salbutamol at 0.6 nmol x kg(-1) x min(-1) and 6.0 nmol x kg(-1) x min(-1) caused increasing but qualitatively similar changes in salivary composition to intracarotid noradrenaline but was less effective than noradrenaline in augmenting salivary protein release. Equimolar intravenous infusions of salbutamol and noradrenaline were equally potent in altering salivary electrolyte concentrations but salbutamol by this route had less effect on protein release and fluid secretion. Concurrent intravenous and intracarotid infusions of beta1-(CGP) and beta2-(ICI) antagonists with intracarotid salbutamol showed that the beta2-antagonist was more potent than the beta1-antagonist by the intracarotid route thereby demonstrating the presence of glandular beta2-receptors and eliminating the possibility that the response to salbutamol was due totally by reflex increases in general sympathetic tone triggered by lowered blood pressure. It was concluded that the kangaroo parotid has functional beta1- and beta2-adrenoreceptor subtypes in endpieces whereas the data provide little support for either adrenoreceptor subtype being present in the excurrent duct system.     

beta-Receptor agonist activity of phenylephrine in the human forearm.

Phenylephrine is generally regarded as a "pure" alpha(1)-agonist. However, after treatment of the forearm with the alpha-adrenergic-blocking drug phentolamine, brachial artery infusion of phenylephrine can cause transient forearm vasodilation. To determine whether this response was beta-receptor mediated, phenylephrine, phentolamine, and propranolol were infused into the brachial arteries of six healthy volunteers. Forearm vascular conductance (FVC) was also calculated and expressed as arbitrary units (units). Infusion of phenylephrine by itself (0.5 microg. dl forearm volume(-1). min(-1)) caused a sustained decrease (P < 0.05) in FVC from 3.5 +/- 0.7 to 0.9 +/- 0.2 units (P < 0.05). Infusion of the alpha-blocker phentolamine increased (P < 0.05) baseline FVC to 5.7 +/- 1.3 units. Subsequent infusion of phenylephrine after alpha-blockade caused FVC to increase (P < 0.05) for ~1 min from 5.7 +/- 1.3 to a peak of 13.1 +/- 1.8 units. Propranolol had no effect on baseline flow, and subsequent phenylephrine infusion after alpha- and beta-blockade caused a small, but significant, sustained decrease in FVC from 5.1 +/- 1.0 to 3.6 +/- 0.8 units. There were no systemic effects from the infusions, and saline infusion at the same rate (1-2 ml/min) had no forearm vasoconstrictor or dilator effects. These data indicate that in humans phenylephrine can exert transient beta(2)-vasodilator activity when its predominant alpha-constrictor effects are blocked.     

Synchronization of secretion of the evoked transmitter quanta as mechanism of the facilitating action of sympathomimetics

Noradrenaline, isoproterenol, dobutamine were found to modulate kinetics of quanta secretion so as to synchronize the transmitter release. This effect could be prevented with blocking agents of beta-adrenoreceptor (atenolol, propranolol). Activators of beta-adrenoreceptors klonidine and phenylephrine did not change the kinetics of quanta secretion, whereas phentolamine did not affect the synchronizing effect of noradrenaline. The change in the time course of the secretion induced by noradrenaline increased the end-plate current amplitude. There seems to exist a specific presynaptic mechanism involving beta-adrenoreceptors for facilitation of effects of sympathomimetics.     

Effect of phenylephrine on lipolysis in rat adipocytes: no evidence for an alpha-adrenergic mechanism

Phenylephrine, a strong alpha 1-adrenergic agonist, exerted a concentration dependent antilipolytic effect against isoproterenol-activated lipolysis in rat adipocytes with the effect decreasing as the isoproterenol concentration increased. The alpha-adrenergic antagonists phentolamine and phenoxybenzamine did not reverse phenylephrine's antilipolytic effect. Phenylephrine alone activated lipolysis at concentrations above 10(-5) M and at 5 X 10(-4) M the rate of lipolysis was increased 3.4-fold. Propranolol abolished this effect. In the presence of sub-maximum concentrations of dibutyryl cyclic-AMP (less than 10(-4) M), 10(-4) M phenylephrine increased the rate of lipolysis above that activated by dibutyryl cyclic-AMP alone. At maximum dibutyryl cyclic-AMP concentrations, or in the presence of propranolol, phenylephrine had no effect on dibutyryl cyclic-AMP-dependent lipolysis. There is no evidence to support an alpha 1-adrenergic mechanism for regulation of lipolysis in the rat adipocyte. All effects of the alpha-adrenergic agonist phenylephrine appear to be due to its weak beta-adrenergic activity.     

Role of alpha-adrenergic stimuli in the control of rat renal ammoniagenesis

The effects of phenylephrine on renal ammoniagenesis and the involvement of Ca2+ in phenylephrine action were investigated in isolated proximal fragments of rat-kidney tubules. Phenylephrine stimulated renal ammoniagenesis from 1 and 2 mM glutamine whereas no significant changes took place at a higher concentration of glutamine (20 mM). Stimulation of ammonia synthesis by phenylephrine was found to be linear with time and dose-dependent between 10(-9) and 10(-4) M. Phenylephrine-stimulated ammoniagenesis was blocked by phentolamine (10 microM) but not by propranolol (10 microM) confirming that the effect is mediated by alpha-adrenergic stimuli. No stimulatory effect of phenylephrine was observed in Ca2+ depleted proximal tubule fragments, suggesting that Ca2+ is required in this adrenergic response.     

Kinetic characteristics of hamster (Mesocricetus auratus) brown fat (Na+/K+)-ATPase: effects of catecholamines

1. The (Na+/K+)-ATPase activity of brown fat membranes is increased by norepinephrine, the physiological mediator of thermogenesis in this tissue. 2. This increased ATPase activity was inhibited approximately 50% by either propranolol (a beta-adrenergic blocker) or phentolamine (an alpha-blocker). 3. The alpha-agonist, phenylephrine and the beta-agonist, isoproterenol, also stimulated the ATPase activity. 4. That these latter effects were receptor-specific is supported by the finding that: (a) l(-)isoproterenol stimulation was inhibited by propranolol but not by phentolamine; (b) d(+)isoproterenol had no stimulatory effect on the ATPase activity; and (c) the l(-)phenylephrine-induced increase was inhibited by phentolamine but not by propranolol. 5. (-)norepinephrine, l(-)isoproterenol and l(-)phenylephrine all decreased the apparent Km for K+ of the (Na+/K+)-ATPase but did not alter the apparent Km for ATP or the Vmax of the reaction.     

Inhibitory effect of norepinephrine on immunoreactive corticotropin-releasing factor release from the rat hypothalamus in vitro

Effects of catecholamines on immunoreactive corticotropin-releasing factor (I-CRF) release from the rat hypothalamus were examined using a rat hypothalamic perifusion system and a rat CRF RIA in vitro. Norepinephrine had a potent inhibitory effect on I-CRF release in a dose-dependent manner at 0.1 nM-1 microM concentrations, but dopamine did not. This inhibitory effect of norepinephrine was completely blocked by propranolol, but only partially blocked by phentolamine. Isoproterenol also had a potent inhibitory effect at 0.01-100 nM concentrations, and a high dose of phenylephrine (10 nM) inhibited I-CRF release. Clonidine did not influence I-CRF release. These results suggest that norepinephrine inhibits I-CRF release mainly through the beta-adrenergic receptor and partially through the alpha 1-receptor.     

Alpha-adrenergic influences on exocrine pancreatic secretion in the rabbit

Action of phenylephrine (35 micrograms/Kg/min) alone or previously blocked by phentolamine (100 micrograms/Kg/min) on exocrine pancreatic secretion of anaesthetized rabbits has been studied, in basal state or under stimulation by secretin (1 C.U./Kg/h) or by the octapeptide of cholecystokinin (OP-CCK) (0.15 Ivy dog units/Kg/h). Phenylephrine increased arterial pressure. This effect was blocked by phentolamine. However no variations were seen in pancreatic blood flow in any of the experimental conditions assayed. Phenylephrine produced a secretin-like effect on hydroelectrolytic secretion in basal conditions. This action was maintained after the infusion of secretin but not after OP-CCK. This effect was not blocked by phentolamine. Phenylephrine increased protein secretion in the basal state, an action that was blocked by phentolamine. After secretin or OP-CCK stimulation phenylephrine did not increase protein secretion. It is concluded that phentolamine blocks the effects of phenylephrine on acinar cells but not on ductular cells.     

The short-term and long-term effects of gamma-irradiation on the inotropic reaction of the myocardium during the activation of alpha- and beta-adrenoreceptors

The contractile function of myocardium was impaired and its inotropic response to stimulation of alpha- and beta-adrenoreceptors decreased at early times (1-30 days) following whole-body gamma-irradiation with a dose of 1.0 Gy. Six months after irradiation the response of the isolated myocardium to stimulation of adrenoreceptors increased to exceed that of intact animals. In a year the reactivity of the myocardium towards alpha-adrenoreceptor agonists remained high and its sensitivity of phenylephrine hydrochloride increased considerably; the response to beta-adrenoreceptor agonists was virtually absent.     

The role of the autonomic nervous system in the depression of parotid salivary secretion during hyperkalaemia in conscious sheep.

The rate of flow and electrolyte concentration of parotid saliva were measured before, during and after intravenous and contralateral intracarotid infusion of KCl (0.5 mol.1(-1)) and NaCl (0.5 mol.1(-1)) at 385-625 mumol. min(-1) for 40 min into 5 sheep. In intact conscious sheep contralateral intracarotid infusion of KCl caused marked depression of salivary secretion in all experiments whereas infusion of NaCl had no consistent effect on flow. Intravenous infusion of KCl into the intact conscious sheep caused a slight depression of salivary secretion but minimum flow was significantly higher than that during intracarotid infusion. When the sheep were anaesthetized salivary flow rates were low and contralateral intracarotid infusion of KCl either had no effect on flow or caused an increase in flow. After ipsilateral cervical sympathectomy contralateral intracarotid infusion of KCl into the conscious sheep caused a marked depression of salivary flow similar to that occurring when the sheep were intact. After section of the secretomotor nerve of the gland salivary flow rates were low and contralateral intracarotid infusion of KC1 had no effect on flow. The salivary flow responses of the sheep were consistent, regardless of whether the KCl infusions were given within 24 h or 1-2 weeks after cervical sympathectomy or secretomotor nerve section. Salivary sodium concentration was negatively correlated with salivary flow in all experiments. It was concluded that potassium acted at a site located in the head but by direct action on the salivary gland. The depression of salivary secretion by hyperkalaemia resulted from a decline in neural activity in the parasympathetic secretomotor innervation of the parotid gland.     

Studies on the alpha-andrenergic activation of hepatic glucose output. II. Investigation of the roles of adenosine 3':5'-monophosphate and adenosine 3':5'-monophosphate-dependent protein kinase in the actions of phenylephrine in isolated hepatocytes.

The effects of the alpha-adrenergic agonist phenylephrine on the levels of adenosine 3':5'-monophosphate (cAMP) and the activity of the cAMP-dependent protein kinase in isolated rat liver parenchymal cells were studied. Cyclic AMP was very slightly (5 to 13%) increased in cells incubated with phenylephrine at a concentration (10(-5) M) which was maximally effective on glycogenolysis and gluconeogenesis. However, the increase was significant only at 5 min. Cyclic AMP levels with 10(-5) M phenylephrine measured at this time were reduced by the beta-adrenergic antagonist propranolol, but were unaffected by the alpha-blocker phenoxybenzamine, indicating that the elevation was due to weak beta activity of the agonist. When doses of glucagon, epinephrine, and phenylephrine which produced the same stimulation of glycogenolysis or gluconeogenesis were added to the same batches of cells, there were marked rises in cAMP with glucagon, minimal increases with epinephrine, and little or no changes with phenylephrine, indicating that the two catecholamine stimulated these processes largely by mechanisms not involving cAMP accumulation. DEAE-cellulose chromatography of homogenates of liver cells revealed two major peaks of cAMP-dependent protein kinase activity. These eluted at similar salt concentrations as the type I and II isozymes from rat heart. Optimal conditions for preservation of hormone effects on the activity of the enzyme in the cells were determined. High concentrations of phenylephrine (10(-5) M and 10(-4) M) produced a small increase (10 tp 16%) in the activity ratio (-cAMP/+cAMP) of the enzyme. This was abolished by propranolol, but not by phenoxybenzamine, indicating that it was due to weak beta activity of the agonist. The increase in the activity ratio of the kinase with 10(-5) M phenylephrine was much smaller than that produced by a glycogenolytically equivalent dose of glucagon. The changes in protein kinase induced by phenylephrine and the blockers and by glucagon were thus consistent with those in cAMP. Theophylline and 1-methyl-3-isobutylxanthine, which inhibit cAMP phosphodiesterase, potentiated the effects of phenylephrine on glycogenolysis and gluconeogenesis. The potentiations were blocked by phenoxybenzamine, but not by propranolol. Methylisobutylxanthine increased the levels of cAMP and enhanced the activation of protein kinase in cells incubated with phenylephrine. These effects were diminished or abolished by propanolol, but were unaffected by phenoxybenzamine. It is concluded from these data that alpha-adrenergic activation of glycogenolysis and gluconeogenesis in isolated rat liver parenchymal cells occurs by mechanisms not involving an increase in total cellular cAMP or activation of the cAMP-dependent protein kinase. The results also show that phosphodiesterase inhibitors potentiate alpha-adrenergic actions in hepatocytes mainly by a mechanism(s) not involving a rise in cAMP.     

Thiol reactivity and the molecular individuality of alpha- and beta-adrenoreceptors in rat liver plasma membranes.

Whether or not alpha- and beta-adrenoreceptors are non-identical binding sites on the same protein is still an open question. We investigated the effects of sulfhydryl reagents and dithiothreitol on the binding of [3H]dihydroalprenolol and [3H]dihydroergocryptine to beta- and alpha-adrenoreceptors of rat liver plasma membranes. Dithiothreitol inhibited the binding of [3H]dihydroalprenolol to the beta-adrenoreceptor, whereas it had no effect on the specific binding of [3H]dihydroergocryptine to the alpha-adrenoreceptor. In contrast, mersalyl, a mercurial SH reagent, readily blocked the alpha-adrenoreceptor and, although to a lesser extent the beta-adrenoreceptor. The interaction of mersalyl with the alpha-adrenoreceptors was almost instantaneous. In contrast, under the same experimental conditions, the inactivation of the beta-adrenoreceptors was much slower (t 1/2 : 7 min). Finally, a marked difference in the accessibility of the SH groups to mersalyl was observed between the alpha- and beta-adrenoreceptors. The presence of 15 microM (-)-epinephrine or 1.5 microM phentolamine was sufficient to prevent the blockade of the alpha-adrenoreceptor by mersalyl, but inactivation of the beta-adrenoreceptor by mersalyl was not modified by 500 microM (-)-epinephrine and was only slightly decreased by 50 microM (-)-propranolol. Thus, the alpha- and beta-adrenoreceptors from rat liver plasma membranes exhibited biochemical differences which may be interpreted in favor of their molecular individuality.     

Effects of epinephrine and norepinephrine on glucose release from chinook salmon (Oncorhynchus tshawytscha) liver incubated in vitro

The effects of two catecholamines, epinephrine (EP) and norepinephrine (NE), on carbohydrate metabolism were studied by incubating chinook salmon liver in vitro. Basal release of glucose over the course of a 5-h incubation was 7.93 +/- 1.70 mumol/g dry weight. Both EP and NE (2 X 10(-7) M) stimulated glucose release rapidly during the first hour. After 5 h, EP and NE significantly increased glucose release over basal levels to 43.55 +/- 9.01 and 32.75 +/- 6.17 mumol/g dry weight, respectively. Epinephrine- and NE-stimulated glucose release was dose dependent, with a minimum effective dose of 10(-9) M. ED50 for both agents was approximately 2 X 10(-7) M; maximal stimulation occurred at 10(-5) M. No difference in potency between the two catecholamines was found. The effects of adrenergic agonists and antagonists were also studied. Alpha-agonists, methoxamine and phenylephrine, had no effect on glucose release. Isoproterenol, a beta-agonist, stimulated glucose release in a manner similar to EP. The beta-antagonist, propranolol, inhibited both catecholamine- and isoproterenol-stimulated glucose release. Alpha-antagonists (phentolamine, prazosin, and yohimbine) had no effect on either catecholamine- or isoproterenol-stimulated glucose release. Epinephrine and NE stimulate glycogen phosphorylase activity; propranolol inhibits catecholamine-stimulated phosphorylase activity. These results indicate that catecholamines stimulate glucose mobilization in salmon liver by promoting glycogenolysis mediated through beta-adrenergic receptors.     

Selective stimulation and blockade of β-adrenergic receptors in the mandibular gland of the red kangaroo, Macropus rufus

Intracarotid infusions of noradrenaline (0.15 nmol · kg⁻¹ · min⁻¹) either alone or accompanied by phentolamine (1.5 nmol · kg⁻¹ · min⁻¹) caused similar-sized increases in salivary protein, magnesium and bicarbonate, and decreases in osmolality, sodium, potassium and chloride whereas intravenous noradrenaline stimulated much smaller responses. Concurrent infusions of the β₁-antagonist, CGP20712A, blocked these noradrenaline-induced changes in salivary composition more effectively than equimolar infusions of the β₂-antagonist, ICI118551, thereby confirming the presence of β₁-adrenoceptors. Intracarotid infusion of salbutamol at 0.15, 0.3 and 1.5 nmol · kg⁻¹ · min⁻¹ caused increasing but qualitatively similar changes in salivary composition, sodium excepted, to intracarotid noradrenaline with 0.3 nmol being most similar quantitatively. Intravenous infusion of salbutamol caused larger changes in salivary composition than equimolar intravenous noradrenaline thereby indicating that the response to salbutamol may, in part, be mediated by reflex increases in general sympathetic tone triggered by lowered blood pressure. Eliminating this hypotensive effect by concurrent intravenous and intracarotid infusions of β₁-(CGP or atenolol) and β₂-(ICI118551) antagonists with intracarotid salbutamol showed that ICI118551 was more potent than the β₁-antagonists thereby demonstrating the presence of β₂-receptors. It was concluded that the kangaroo mandibular has functional β₁- and β₂-adrenoceptor subtypes in both endpieces and excurrent ducts and that the duct system has two populations of cells, each expressing one receptor subtype. Accepted: 26 July 2000     

Role of sodium and water excretion in the antihypertensive effect of vasopressin in the spontaneously hypertensive rat.

Mean arterial pressure (mmHg (1 mmHg = 133.322 Pa)), sodium excretion rate (mumol.kg-1.min-1), and urine flow (microL.kg-1.min-1) were measured in conscious unrestrained spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY) before, during, and after a 3-h intravenous infusion of arginine vasopressin (20 ng.kg-1.min-1), an equipressor dose of phenylephrine, or an infusion of the vehicle. Cessation of the phenylephrine infusion was associated with a return of arterial pressure to preinfusion control values in both SHR and WKY. Cessation of the vasopressin infusion was also associated with a return of arterial pressure to preinfusion values in WKY. In contrast, in the SHR, arterial pressure fell from a preinfusion control level of 164 +/- 6.2 to 137 +/- 4 mmHg within 1 h of stopping the vasopressin infusion. Five hours after stopping the infusion, pressure was 134 +/- 3 mmHg (29 +/- 5 mmHg below preinfusion levels). Similar to the WKY, cessation of a vasopressin infusion was associated with a return of arterial pressure to preinfusion values in Sprague-Dawley rats. Thus, the failure to observe a hypotensive response in normotensive rats was not a peculiarity of the WKY strain. Sodium excretion rates increased during the infusions of vasopressin to a greater extent in SHR than in WKY. However, the natriuresis induced by phenylephrine was not significantly different from that generated by vasopressin in SHR, and in WKY, the natriuresis was greater for phenylephrine than for vasopressin. Urine output increased to a greater extent during the infusions of phenylephrine in both SHR and WKY than during vasopressin infusion.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of beta-antagonists on isoprenaline-induced secretion of fluid, amylase and protein by the parotid gland of the red kangaroo, Macropus rufus

Selective and non-selective beta-adrenoceptor antagonists were used to block the increases in fluid, protein and amylase secretion caused by sympathomimetic stimulation of the parotid gland of red kangaroos during intracarotid infusion of isoprenaline. ICI118551 at antagonist/agonist ratios up to 300:1 caused increasing but incomplete blockade of fluid secretion, and protein/amylase release. Atenolol at antagonist/agonist ratios up to 300:1 was only marginally more potent than ICI118551 at blocking the fluid, protein and amylase responses. Propranolol at antagonist/agonist ratios of 30:1 was as effective at blocking fluid and protein secretion as the highest ratios of either atenolol or ICI118551. Simultaneous administration of atenolol (30:1) with ICI118551 (30:1) was not as potent as propranolol (30:1). Thus, the beta-adrenoceptor/s in the acini of the kangaroo parotid gland appear to have antagonist-binding affinities atypical of those found for eutherian tissues. The data are consistent with the gland possessing either a single anomalous beta-adrenoceptor or functional beta(2)-receptors in addition to the beta(1)-receptors which are characteristic of eutherian salivary glands.     

Mechanisms of serotonin effect on motility of ileocaecal zone in alert rabbits

I.V. administration of serotonin (2 mg kg(-1)) to alert rabbits changed the ileal, caecal, and colon motility including excitatory and inhibitory components. Initial rise of contractile activity was quickly replaced by its diminishing followed by a longer enhancement of the motility, and then by the final, inhibitory, phase. Under blockade of beta1- and beta2-adrenoreceptors with propranolol inhibition of ileal and caecal contractile activity with serotonin was preserved, the effect of circulating catecholamines on beta-adrenoreceptors of smooth muscle cells seems to be excluded as a cause of the serotonin inhibitory effect. In conditions of blockade of pre- and postsynaptic alpha-adrenoreceptors with phentolamine, there was no significant diminishing of the contractile activity in the ileo-caecal zone below the initial level induced by serotonin in control experiments. Intensification of the ileo-caecal zone contractile activity under the effect of serotonin persisted in conditions of blockade of muscarinic cholinoreceptors and was proceeding with participation of non-cholinergic excitatory mechanism.     

Evidence that rat pineal thyroxine 5'-deiodinase is primarily stimulated by beta- and not alpha-adrenergic agonists and that its adrenergic-stimulated and spontaneous rhythmic nocturnal rise require RNA and protein synthesis

Pineal thyroxine 5'-deiodinase (5'-D) activity rose greater than 10-fold above the basal level 2-3 hr after 1 mg/kg isoproterenol and returned to near the basal level by 6 hr. The same dose of norepinephrine or phenylephrine was without effect, but phenylephrine modestly potentiated isoproterenol-stimulated 5'-D activity. Either actinomycin D or cycloheximide treatment markedly decreased diurnal isoproterenol stimulation and the spontaneous rhythmic nocturnal rise of pineal 5'-D. The data indicate that pineal 5'-D activity is very similar to pineal serotonin N-acetyl transferase in being primarily stimulated by beta-adrenergic agonists and requiring new RNA and protein synthesis for its activation.     

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.