Isoproterenol Dose-response Curve Research Articles

Time course of sympathetic denervation supersensitivity in canine ventricular recovery

We studied the timing of the electrophysiological effects of sympathetic supersensitivity with chronically implanted electrodes in the anterior and posterior left ventricular free wall in 10 dogs. We produced denervation of the anterior wall in six dogs by application of phenol surrounding the anterior electrode. Drug infusions that were performed under pentobarbital sodium anesthesia included norepinephrine, isoproterenol, and methoxamine. In four controls there was no difference in response of the two sites. Presynaptic supersensitivity was manifest as early as 2 days and as late as 64 days by a parallel left shift (greater than or equal to 8.3 ms) in the norepinephrine dose to effective refractory period shortening response curve in the anterior compared with posterior left ventricle, P less than 0.01. The isoproterenol dose-response curve was also shifted to the left by 5.6 ms (P less than 0.01) but was manifest only after 10 days and only until 28 days from the denervation procedure. Local repolarization in the denervated areas shortened more than the innervated areas with both drugs. The methoxamine dose-response curve was flat, and the anterior-denervated area was not different than the posterior-innervated area. We conclude that recovery properties in ventricular muscle demonstrate evidence of supersensitivity, which is neurotransmitter and beta- but not alpha-receptor specific.

Additive effect of theophylline on the cardiac response to isoproterenol.

To ascertain the effect of theophylline on the cardiac chronotropic response to beta-adrenergic stimulation, isoproterenol dose-response curves in healthy young subjects were compared during saline and theophylline maintenance infusions. Each study was repeated 1 to 3 weeks later to evaluate reproducibility. Neither the dose of isoproterenol required to raise the heart rate by 25 bpm (2.32 +/- 0.81 vs. 1.55 +/- 0.46 micrograms on day 1 and 1.28 +/- 0.22 vs. 1.27 +/- 0.25 micrograms on day 2) nor the slopes of the dose-response curves were affected by theophylline. Higher heart rates were observed after isoproterenol bolus dosing during theophylline than during saline infusion because of additive chronotropic effects of theophylline and isoproterenol. Since theophylline does not interact in a synergistic fashion with isoproterenol, phosphodiesterase inhibition appears to be an unlikely mechanism of the chronotropic effect of methylxanthines at therapeutic concentrations.

Autonomic control of ventricular tachycardia: Direct effects of beta-adrenergic blockade in 24 hour old canine myocardial infarction

The purpose of this study was to determine whether alpha- or beta-adrenergic influences directly modulate the rate of spontaneous ventricular tachycardia occurring 24 hours after left anterior descending coronary artery occlusion. Chloralose-anesthetized, open chest dogs (n = 41) with ventricular tachycardia were studied. The left anterior descending artery was cannulated distally. Neither intracoronary saline solution nor phenylephrine (0.3 to 12 micrograms) changed the rate of ventricular tachycardia; however, isoproterenol (0.01 to 10 micrograms) produced dose-dependent increases in the rate. In six dogs, metoprolol, 5 mg given intravenously, slowed ventricular tachycardia from 174 +/- 10 (mean +/- SE) to 140 +/- 17 beats/min (p less than 0.05). This was accompanied by decreases in mean arterial pressure from 106 +/- 7 to 95 +/- 8 mm Hg, cardiac output from 2.6 +/- 0.3 to 1.6 +/- 0.3 liters/min and prolongation of atrioventricular conduction from 134 +/- 10 to 189 +/- 29 ms (all p less than 0.05) during atrial pacing at a cycle length of 300 ms. In 10 dogs, metoprolol (0.5 mg) given intracoronary, a dose that shifted the isoproterenol dose-response curve to the right, slowed ventricular tachycardia from 174 +/- 7.2 to 140 +/- 9.7 beats/min (p less than 0.05) without hemodynamic changes. Additional metoprolol (4.5 mg) given intravenously produced hemodynamic alterations, but ventricular tachycardia did not slow further. Therefore, beta- but not alpha-adrenergic influences control the rate of ventricular tachycardia occurring 24 hours after left anterior descending coronary artery occlusion. Furthermore, beta-adrenergic blockade slows ventricular tachycardia solely by a direct electrophysiologic effect on the tachycardia foci and not indirectly as a result of hemodynamic effects.

Canine cardiovascular responses to endotracheally and intravenously administered atropine, isoproterenol, and propranolol

This study compared canine cardiovascular responses observed after endotracheally administered atropine, isoproterenol, and propranolol to those observed following IV administration. Acetylcholine and isoproterenol dose response curves for arterial pressures and heart rate were established following IV boluses of each drug. Once the dose response curves were established, atropine and propranolol were administered endotracheally and intravenously in different groups to alter the established dose response curves. The time required for endotracheally and intravenously administered atropine and propranolol to inhibit 50% of the mean arterial pressure response following an IV infusion of acetylcholine and isoproterenol, respectively, was determined. Atropine and propranolol administered by either route significantly altered the arterial pressure response to acetylcholine and isoproterenol (P less than .05), respectively. Atropine altered the heart rate response to acetylcholine when administered by either route (P less than .05). IV-administered propranolol altered the heart rate response to isoproterenol (P less than .05); endotracheally administered propranolol did not. Atropine administered IV inhibited 50% of the mean arterial pressure response during an acetylcholine infusion within 21 seconds, and within 48 seconds following endotracheal administration. Propranolol administered intravenously inhibited 50% of the mean arterial pressure response during an isoproterenol infusion within 23 seconds, and within 49 seconds following endotracheal administration. The arterial pressure and heart rate responses immediately following endotracheally and intravenously administered isoproterenol also were measured and compared. The arterial pressure and heart rate responses after endotracheally administered isoproterenol were much less than those following IV administration (P less than .005). In dogs the pharmacological effects following endotracheally and intravenously administered atropine and propranolol are similar, while the effects of endotracheally and intravenously administered isoproterenol differ greatly.

Effect of depletion of phosphate and bicarbonate ions on insulin action in rat adipocytes.

The effect of insulin on rat adipocytes was studied in isotonic buffers (pH 7.4) containing NaCl, CaCl2, MgSO4, KCl, and bovine serum albumin but no phosphate or bicarbonate anions. In phosphate- and bicarbonate-free buffers the dose-response curve to insulin is shifted to the right, the effects of the hormone on hexose uptake, glucose metabolism, and inhibition of lipolysis being observed at much higher (nearly 2 orders of magnitude) concentrations of insulin. The insulin binding capacity of the cells is only slightly changed. The dose-response curve for isoproterenol which stimulates lipolysis in the same cell type is almost the same in both Krebs-Ringer bicarbonate buffer and phosphate- and bicarbonate-free buffers. The dose-response curves for agents that mimic the action of insulin such as wheat germ agglutinin or vanadate ions are also shifted to the right. The dose-response curve to insulin can be returned to "normal" by readdition of either bicarbonate or phosphate. Almost complete recovery is obtained at either 10 mM bicarbonate or 24 mM phosphate, respectively. External Ca2+ ions which are not required for the proper action of insulin in fat cells maintained in Krebs-Ringer bicarbonate buffer, become essential for insulin action in bicarbonate-free buffer. The study indicates that depletion of bicarbonate and, to a lesser extent, phosphate anions, interferes with an essential insulin-dependent post-binding event. Also, in bicarbonate-free medium, external Ca2+ ions are essential for insulin-mediated processes. The implications of this study to the mode of action of insulin, and to physiological and clinical states of insulin desensitization are discussed.

Defibrotide, an Antithrombotic Substance That Preserves Postsynaptic α- and β-Adrenergic Function in Post Acute Infarcted Rabbit Hearts

Defibrotide, a simple strand polydeoxyribonucleotide of mammalian origin with a molecular weight of 20,000 daltons, given intravenously to the rabbit before and after production of left ventricular infarction, prevents the alteration of the contractile response to postsynaptic adrenergic stimulation tested in isolated perfused heart preparations 3 days after coronary artery occlusion. According to the dose-response curves for isoproterenol and tyramine, left ventricular dP/dtmax was significantly depressed in infarcted hearts, whereas the dose-response curve for the inotropic effect of phenylephrine was markedly enhanced. These alterations were prevented by pretreatment of the rabbits with defibrotide (32 mg/kg/h i.v. for 6 h). In fact the potency ratios, calculated from the dose-response curves related to dP/dtmax of isoproterenol, tyramine, and phenylephrine in infarcted and control hearts excised from defibrotide treated and shamoperated rabbits, are nearly 1. The observed alterations in myocardial contractility in infarcted hearts seem to be specific for postsynaptic alpha and beta-adrenoceptors since the dose-response curve of left ventricular dP/dtmax for histamine is not different from control. The results obtained with defibrotide reflect the ability of this substance to protect the myocardial tissue from ischemic damage: this is also supported by the capacity of defibrotide (8 mg/kg/h i.v. for 6.5 h) to prevent the reduction of CPK-activity in the infarcted ventricle. Finally, we suggest that the observed beneficial effect of defibrotide in rabbit heart may also be explained by the antithrombotic effect of this substance, which is based on its profibrinolytic activity and PGI2-release.

Double-Blind Comparison of the β1-Selectivity of Single Doses of Bisoprolol and Atenolol

The beta 1-adrenoceptor selectivity of bisoprolol (BPL) was investigated using the forearm circulation of eight healthy subjects. Each subject was studied twice, with at least 10 days in between each investigation. A brachial artery was cannulated for intra-arterial (i.a.) monitoring of blood pressure and for i.a. infusion of isoproterenol (ISO) and epinephrine (EPI). ISO was given in doses of 0.02-0.10-0.40 and 1.20 ng/kg/min, for 3 min per dose. After 20 min rest, EPI was infused in doses of 0.08 and 2.0 ng/kg/min for 6 min per dose. Subsequently, the subjects received an oral dose of either 20 mg BPL or 100 mg atenolol (ATL), and 2 h later, the ISO and EPI infusions were repeated. Forearm blood flow was measured by venous occlusion strain-gauge plethysmography. ISO produced a dose-dependent vasodilatation, whereas the response to EPI varied between individuals. After administration of BPL and ATL, the ISO dose-response curves were shifted to the right by 2.8 and 2.6 times, respectively (both p less than 0.01). Both beta-blockers influenced the vascular effect of EPI in the direction of vasoconstriction. However, this was only significant for ATL (p less than 0.05). From the latter observation it is concluded that BPL is slightly more beta 1-adrenoceptor-selective than ATL, using the forearm vascular bed.

Plasma concentration-response relationships of two formulations of propranolol.

The time-course of beta blockade induced by two formulations of propranolol was compared to their plasma concentration-time curves. Graded infusions of isoproterenol were used to assess the degree of beta blockade at different times after oral administration of 80 mg of propranolol to 11 healthy volunteers. The time-course of drug effect was measured as the decline of the systolic pressor dose 20 (SPD 20) and the chronotropic dose 20 (CD 20). Variability of plasma propranolol concentration was small, varying within subjects from 27% to 36% and between subjects from 19% to 28% at the various sampling times. Pharmacodynamic effects showed a similar reproducibility: intra-individual variation was 15% to 28% for CD 20 and 17% to 32% for SPD 20; interindividual variation was 10% to 24% for CD 20 and 13% to 23% for SPD 20. Pooling of the data of all subjects indicated a parallel decline of drug concentration and effect. However, three of the 11 subjects showed drug effects declining at a faster rate than drug levels. This dissociation between serum concentrations and effects points out the clinical relevance of complementing kinetic studies of propranolol with pharmacodynamic studies. The good reproducibility within subjects and the small interindividual variation suggests that isoproterenol dose-response curves may be a useful tool for such studies.

Effects of magnesium on the action of vasodilatory agents.

Studies have shown that alterations of the magnesium (Mg2+) concentration can alter the response of certain vasoactive compounds. Responses of rabbit thoracic aorta to verapamil, diltiazem, nitroglycerin and isoproterenol were examined in zero Mg2+ (0.0 M), N Mg2+ (1.2 mM), 2 N Mg2+ (2.4 mM) and 4 N Mg2+ (4.8 mM). Preconstriction was induced with norepinephrine and cumulative dose-response curves were obtained for the vasodilators. The dose-response curve for isoproterenol was shifted to the right in zero Mg2+ while there was no effect on the other vasodilators. Elevation of the Mg2+ concentration to 4.8 mM produced a shift to the left in the dose-response curves for diltiazem, nitroglycerin and isoproterenol with no effect on verapamil. Therefore, Mg2+ deficiency does not appear to affect the vasodilatory actions of the agents tested except for the beta-receptor agonist, isoproterenol. Elevated Mg2+, however, potentiated the actions of isoproterenol, nitroglycerin and diltiazem, but not verapamil.

Phentolamine and rat aortic smooth muscle responsiveness to potassium chloride, isoproterenol and norepinephrine.

Rat aortic smooth muscle responsiveness to potassium chloride and isoproterenol in the presence of the alpha-adrenergic blocker phentolamine was investigated. A A significant decrease in the response of the vascular smooth muscle of aorta to low concentrations of potassium chloride (KCl; 8-12 mM) in the presence of phentolamine was observed. However, no effect of phentolamine was seen at KCl concentrations greater than 16 mM. Isoproterenol-induced relaxation was significantly increased in aortic smooth muscle incubated with phentolamine. Phentolamine also attenuated the contraction induced by high concentrations of isoproterenol. No long-lasting effect of the alpha-adrenergic blocker was apparent since the response to norepinephrine was not altered following a 1-hour washout of phentolamine after the isoproterenol dose-response curve. The results of this study suggest that: (i) phentolamine has no long-lasting effects on rat aortic smooth muscle; (ii) since the rat thoracic aorta has a sparse adrenergic innervation, the decrease in responsiveness to KCl in the presence of phentolamine is most likely due to a nonspecific effect on the vascular smooth muscle as opposed to blocking the effects of norepinephrine released from adrenergic nerve terminals, and (iii) the increased relaxation response to isoproterenol may be due to a blockade of the alpha-receptors activated by isoproterenol.

Isoproterenol-induced desensitization to the positive inotropic effect of isoproterenol in ventricular strips isolated from carp heart ( Cyprinus carpio)

1. Whether the positive inotropic effect of isoproterenol in ventricular strips of carp heart is altered by previous exposure to the agonist was studied. 2. Isoproterenol produced a concentration-dependent positive inotropic effect in these preparations which was competitively antagonized by propranolol. 3. Isoproterenol dose-response curves were shifted significantly downward and to the right after previous treatment with and removal of isoproterenol. 4. The desensitization could be demonstrated after 5 min incubation and near maximal desensitization was observed after 30 min exposure to 1000 nM isoproterenol. The responsiveness was only partially recovered after 180min incubation in drug-free medium. 5. Isoproterenol produces a rapidly developing desensitization to inotropic effects of the beta-adrenergic agonist. This phenomenon may be mediated by alterations in beta-adrenergie receptors, adenylate cyclase and/or the beta receptor-adenylate cyclase coupling mechanism.

Age-dependent changes in electrophysiologic characteristics of fast and slow action potentials in rat papillary muscle.

Isolated papillary muscles from juvenile (about 2 months old, average weight of 250 g) and young adult rats (about 4 months old, average weight 485 g) were studied for age-dependent differences in the characteristics of fast and slow action potentials (APs). The fast and slow APs were recorded in 5.4 mM and 25 mM K+-Tyrode solutions, respectively (stimulation rate of 1 Hz). For the slow APs, the dose-response curves for isoproterenol versus Vmax (the maximum rate of rise of the APs), overshoot, and AP amplitude were linear between 10(-9) M and 10(-6) M (10(-5 M in some cases) in the juvenile and young adult rats. Isoproterenol pretreatment (1 mg/kg s.c., 1 h prior) decreased the slope of the dose-response curve, and saturation was achieved at a lower concentration. The Vmax, overshoot, and amplitude of both the fast and slow APs were somewhat smaller in the young adult rats than in the juvenile rats; there were no differences in the resting potential, AP duration, or threshold voltage. These results suggest that activation of a greater fraction of the beta-adrenergic receptors is coupled directly or indirectly to activation of a greater fraction of the slow channels. The pretreatment data suggest that down-regulation of the beta-adrenergic receptor may occur. The conductance per channel for the fast Na+ channels and slow channels, and (or) the number of both types of functional channels, may decrease with age.

The effect of the beta-adrenoreceptor antagonist Ro03-7894 on rat atrial tension development and (−)-[ 3H]dihydroalprenolol binding to cardiac and lung membranes

The ability of 1-(5-chloracetylaminobenzfuran-2-yl)-2-isopropylaminoethanol (Ro03-7894) to irreversibly inactivate beta-adrenoreceptors was studied. In isolated rat atria Ro03-7894 (500 μM) depressed and shifted the tension development curve for isoproterenol to the right. After a 2 hour washout period the dose response curve for isoproterenol was further depressed. At a lower dose of Ro03-7894 (50 μM), the isoproterenol dose response curve was also depressed and shifted to the right although after a 2 hour washout, the sensitivity to isoproterenol was restored but the maximum response was still depressed. Ro03-7894 (50 μM) also depressed the tension development response to increasing concentrations of external calcium. The concentration of Ro03-7894 that inhibited (−)-[ 3H]dihydroalprenolol (DHA) binding by 50% in cardiac and lung membranes was 20 μM. Incubation of rat ventricular or lung membranes for 1 hour with 100 μM Ro03-7894 followed by washing did not change the concentration of beta-adrenoreceptors or the K D values for [ 3H]DHA binding. Furthermore, neither the concentration of beta-adrenoreceptors nor the K D for [ 3H]DHA binding was changed in cardiac and lung membranes at 4 or 24 hours after an i.p. injection of 20 mg/kg of Ro03-7894. The results suggested that Ro03-7894 was a relatively weak beta-adrenoreceptor antagonist which under the conditions used did not irreversibly inactivate the receptor but probably depressed tension development in intact atria nonspecifically.

Evidence that beta 1-adrenoceptor activation mediates isoproterenol-stimulated renin secretion in the rat.

The goal of these experiments was to determine if isoproterenol-stimulated renin secretion in the rat is mediated by activation of beta 1- and/or beta 2-adrenoceptors. The rat renal cortical slice preparation was used. The renin secretory rate was a sigmoid function of the logarithm of the isoproterenol concentration; half-maximal and maximal stimulation occurred at approximately 0.01 and 0.1 microM isoproterenol, respectively. Neither timolol (a nonselective beta-antagonist) nor atenolol (a beta 1-selective antagonist) had a significant effect on basal secretory rate, but both shifted the isoproterenol dose-response curve to the right without changing its slope, suggesting competitive antagonism. Timolol was the more potent, but the response to a maximally effective concentration of isoproterenol could be blocked by timolol (0.9 microM), atenolol (110 microM), or a combination of the two (0.45 microM timolol plus 55 microM atenolol). This latter finding is consistent with action of the two antagonists at one and the same site. If it is assumed that timolol antagonizes both beta 1- and beta 2-adrenoceptors and that atenolol antagonizes only beta 1-adrenoceptors, it follows that isoproterenol-stimulated renin secretion in this preparation is mediated by activation of beta 1-adrenoceptors.

Reconstitution of a hormone-sensitive adenylate cyclase with membrane extracts from Neurospora and avian erythrocytes.

Adenylate cyclase activity associated to wild type Neurospora membranes is highly dependent on Mn2+ and insensitive to fluoride, guanyl nucleotides, and cholera toxin. These membranes are able to interact with components of detergent extracts from turkey erythrocyte ghosts. The reconstituted cyclase system is catalytically active in the presence of Mg2+ and it is activated by guanyl-5'-yl imidodiphosphate plus isoproterenol and fluoride. When detergent extracts were prepared from avian erythrocyte membranes treated with cholera toxin, the reconstituted system was stimulated by guanyl-5'-yl imidodiphosphate in the absence of isoproterenol and cyclase activities were higher than those observed with extracts from membranes not treated with the toxin. Dose-response curves for isoproterenol and fluoride in the reconstituted system were similar to those reported for avian erythrocyte and liver membranes, respectively.

In vitro contractile responses of the uterus from ‘restricted diet’ rats to adrenoceptor agonists. Influence of cyclo-oxygenase inhibitors

The experiments concerned the effects of 15 days of restricted diet (50% of the normal food intake) on the magnitude of phasic contractions (Isometric Developed Tension, IDT) of uterine horns isolated from estrous rats. During 60 min following isolation, the IDT of normally fed controls diminished significantly whereas preparations from animals on the restricted diet had a better contractile constancy. This improved motility was prevented by blockers of prostaglandin (PG) synthesis as well as by return to a normal diet. Cumulative dose-response curves for isoproterenol, norepinephrine and methoxamine were made for the different groups. Isoproterenol and norepinephrine evoked a dose-dependent inhibition of IDT. This response was significantly shifted to the right with uteri from restricted diet animals. Following incubation with propranolol, norepinephrine stimulated the magnitude of contractions significantly more in uterine horns from restricted diet rats than in those from controls. The dose-response curve showing the enhancement of motility induced by methoxamine was displaced tothe left in preparations from animals on a restricted diet. This shift was abolished by restoring the normal diet as well as by the presence in vitro of indomethacin or acetylsalicylic acid. The results suggest that tissue PGS, the prevalence of α-adrenoceptor mechanisms and the reduction of β-ones, are involved in the contractile behavior of the uterus isolated from restricted diet rats.

Potentiation of slow action potentials with theophylline or "micro" adenosine deaminase.

The effects of endogenous adenosine on rat atrial and ventricular slow action potentials (AP) were studied using theophylline, an adenosine receptor antagonist, or "micro" adenosine deaminase (mADA), small polypeptides having adenosine deaminase activity. Exogenous adenosine (10(-6) M) depressed slow APs at low and high isoproterenol concentrations and shifted the isoproterenol dose-response curve to the right in the atrium. In the ventricle, exogenous adenosine inhibited slow APs at low isoproterenol doses and only shifted the bottom of the dose-response relationship to the right. mADA (0.84 U) or theophylline (5 X 10(-5) M) potentiated the response to threshold concentrations of isoproterenol and caused a parallel shift of the curve to the left in the atrium but only shifted the bottom portion of the curve in the ventricle. This potentiation of slow APs in the presence of mADA or theophylline suggests that endogenous adenosine attenuates the response to isoproterenol in cardiac muscle.

The ratio of cardiac to vascular beta-receptor blockade of atenolol and propranolol in spontaneously hypertensive rats in vivo.

Ratios of cardiac to vascular beta-receptor blockade (C:V ratios) of atenolol and propranolol were determined in pentobarbital anesthetized spontaneously hypertensive (SHR) rats. These values and the cardiovascular responses to isoproterenol were compared with those of age-matched normotensive control (Donryu, DON) rats reported previously. Mean blood pressure (BP) and heart rate (HR) were recorded. Full dose-response curves for isoproterenol were constructed in BP and HR. In vivo pD2 values of isoproterenol (potencies), were not different between DON and SHR rats, although the maximal responses to isoproterenol (efficacy) were significantly suppressed in SHR rats. C:V ratios of atenolol and propranolol in SHR rats were 7.95 and 0.44, respectively. As the values in DON rats were 9.77 and 1.20, respectively, C:V ratios of atenolol and propranolol were decreased in SHR rats. Markedly decreased C:V ratios of propranolol in SHR rats may explain its relatively weak antihypertensive action.

Unaltered lymphocyte beta-adrenoceptor responsiveness in hyperthyroidism and hypothyroidism.

Beta adrenoceptor sensitivity may be altered in thyrotoxicosis and myxedema. We therefore studied beta-adrenoceptor responses of peripheral blood lymphocytes to stimulation with 10(-9) to 10(-6) M (-)-isoproterenol from patients before and after treatment of myxedema and thyrotoxicosis as well as in patients without thyroid disease. There were six patients in each group. Lymphocyte basal cyclic adenosine monophosphate (cAMP) concentrations were higher in untreated thyrotoxicosis (4.94 +/- 0.46 pmole/10(6) cells) than in controls (3.47 +/- 0.42 pmole/10(6) cells, p less than 0.05) and in untreated myxedema (3.11 +/- 0.50 pmole/10(6) cells, p less than 0.025). The full isoproterenol dose-response curves were similar in all groups. Calculated maximum velocity (Vmax) showed an approximate increase in cAMP of 14.5 pmole/10(6) cells. Isoproterenol concentrations at half-maximum velocity (EC50) were approximately 10(-8) M. It is concluded that lymphocyte beta 2-adrenoceptor responses are not altered in hypothyroidism and hyperthyroidism.

β-adrenergic regulation of rat parotid gland exocrine protein secretion during aging

β-Adrenergic regulation of exocrine protein secretion from the parotid gland was studied over the adult rat life span. Enzymatically dispersed cell aggregates were prepared from 3−, 6−, 12−, and 24-month-old rats and exocrine protein secretion (amylase release) measured. No age differences were seen in the time course of amylase release following (−)-isoproterenol stimulation or in the (−)-isoproterenol dose-response curve. The β-adrenergic antagonist (±)-propanolol inhibited (−)-isoproterenol-stimulated protein secretion from parotid cell aggregates of young and old animals equally. Similarly dibutyryl cyclic AMP induced comparable rates of protein secretion from cells of different aged rats. Direct examination of β-adrenergic receptor characteristics in parotid gland membranes from 3- to 24-month-old rats revealed no differences in the equilibrium dissociation constant ( K d) or maximum specific ligand binding capacity (receptor number). These results suggest that the rat parotid β-adrenergic system remains functionally intact throughout the animals' lifetime.