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At least 271 records · Page 15Linked to original sources
PubMed1988

Facilitatory presynaptic angiotensin receptors on the sympathetic nerves of the human saphenous vein and pulmonary artery. Potential involvement in beta-adrenoceptor-mediated facilitation of noradrenaline release.

Spirally cut strips of human saphenous vein and pulmonary artery preincubated with 3H-noradrenaline were superfused in the presence of corticosterone and desipramine or cocaine. In the saphenous vein angiotensin I, angiotensin II and angiotensin III concentration-dependently increased the electrically (2 Hz) evoked tritium overflow (relative order of potency: angiotensin II greater than angiotensin I greater than angiotensin III). The angiotensin receptor antagonist saralasin displaced the concentration-response curve of angiotensin II to the right, and also blocked the facilitatory effect of angiotensin III. Captopril, an inhibitor of angiotensin converting enzyme, did not modify the concentration-response curve of angiotensin I and did not significantly diminish the release-increasing effect of the nonselective beta-adrenoceptor agonist isoprenaline, whereas saralasin attenuated the facilitatory effect of the beta 2-adrenoceptor agonist procaterol. In the pulmonary artery the angiotensin receptor agonist Val5-angiotensin II-Asp1-beta-amide also increased the electrically evoked tritium overflow in a concentration-dependent manner. It is concluded that the sympathetic nerve fibres of the human saphenous vein (and probably of the human pulmonary artery as well) are endowed with facilitatory presynaptic angiotensin receptors. Angiotensin I exerted its facilitatory effect in the saphenous vein probably via direct stimulation of angiotensin receptors but not by conversion to angiotensin II. Furthermore, the beta 2-adrenoceptor-induced facilitation of noradrenaline release may in part be mediated by local stimulation of angiotensin II synthesis, which may occur by increased formation or activation of renin and/or increased availability of angiotensinogen.

Adrenergic Fibers↗
PubMed1987

Reduction with age in the relaxation to beta-adrenoceptor agonists and other vasodilators in rat aorta.

We have examined the relaxation produced by the beta-adrenoceptor agonists isoprenaline and procaterol, and by sodium nitroprusside, forskolin and isobutylmethylxanthine in KCl (40 mmol/l)-contracted aortae from 6 week, 3 month and 6 month old Sprague-Dawley rats. The maximum relaxation to all agents was greatest in aortae from 6 week old animals. The relaxation to the beta-adrenoceptor agonists was virtually abolished, and the relaxation to the other agents significantly reduced, in aortae from 3 and 6 month old animals. There were no significant differences in the response to any agent between aortae from 3 and 6 month old animals, so that the changes seen occurred in maturation from 6 week to 3 month. The reduced vasodilator response does not occur at the level of the beta-adrenoceptor or adenylate cyclase, since the response to sodium nitroprusside was also affected, but is a general reduction in the ability of the aorta to relax.

Adrenergic beta-Agonists↗
PubMedDate not supplied

Hypertrophic responsiveness to beta 2-adrenoceptor stimulation on adult ventricular cardiomyocytes.

The aim of the present study was to characterize the receptor subtype and the second messenger involved in the newly discovered hypertrophic effect of beta-adrenoceptor stimulation in cultures of adult ventricular cardiomyocytes. Cardiomyocytes isolated from adult rats and cultured for 6 days in presence of 20% fetal calf serum (FCS) were used as experimental model. Hypertrophic responsiveness of cardiomyocytes was characterized by rate of protein synthesis, increase in protein mass, and increase in RNA content. The hypertrophic effect of the non-specific beta-adrenoceptor agonist isoprenaline was abolished in presence of a specific beta 2-adrenoceptor antagonist (ICI 118,551), could be mimicked by use of a beta 2-adrenoceptor agonist (procaterol) or direct stimulation of adenylate cyclase (forskolin) or addition of a cell-permeable analogue of cAMP (dibuytyrylcyclo-AMP). In presence of Rp-cAMPS, an inhibitor of protein kinase A, the hypertrophic effect of isoprenaline was abolished. The results indicate that the hypertrophic effect of beta-adrenoceptor stimulation is due to stimulation of beta 2-adrenoceptors and activation of adenylate cyclase and protein kinase A.

Adenylyl Cyclases↗
PubMed1982

Cardiostimulatory effects of prenalterol, a beta-1 adrenoceptor partial agonist, in vivo and in vitro. Correlation between physiological effects and adenylate cyclase activity.

The cardiostimulatory effects of prenalterol, a beta-1-adrenoceptor partial agonist, were studied in vivo and in vitro and compared to those evoked by isoprenaline, a full agonist, and to those of other partial agonists. In the anaesthetized rat, prenalterol and terbutaline were found not to elevate the myocardial cyclic AMP content; this was in sharp contrast to isoprenaline. Both partial agonists did, however, produce significant effects on heart rate. In the anaesthetized cat, prenalterol exhibited chronotropic and inotropic intrinsic activities of 88 and 76% respectively in relation to isoprenaline. No statistically significant increase in myocardial cyclic AMP content could however be detected. Prenalterol did not stimulate adenylate cyclase significantly in the cat myocardial homogenate. This was also true of the beta-2-adrenoceptor selective partial agonist procaterol. In this preparation, isoprenaline, noradrenaline and adrenaline acted as full agonists. Furthermore, prenalterol produced a concentration-dependent inhibition of isoprenaline-activated adenylate cyclase. Our data indicate that maximal cardiac stimulation occurs at a low level of adenylate cyclase activation and low myocardial cyclic AMP concentration when provoked by a full beta-adrenoceptor agonist. The maximal physiological effects of a partial agonist such as prenalterol may consequently be achieved at a marginal activation of the adenylate cyclase. The present data may thus support the hypothesis of a large beta-adrenoceptor reserve for full agonists in the heart.

Adenylyl Cyclases↗
PubMed1979

Pharmacological characteristics of beta-adrenoceptor binding sites in intact and sympathectomized rat spleen.

[3H]-(--)-Dihydroalprenolol ([3H]-DHA) binds to rat spleen membranes with a dissociation equilibrium constant (KD) of about 0.7 nM and a maximal number of binding sites of 272 fmoles x mg protein-1. Approximately 90% of the sites labelled by 1 nM [3H]-DHA possess classical properties of beta-adrenoceptors. The labelled ligand is stereospecifically displaced by the isomers of propranolol and the order of potency of agonists is: isoprenaline greater than adrenaline greater than noradrenaline. Highly selective beta 1 antagonists such as practolol and atenolol displaced [3H]-DHA from spleen membranes in a biphasic manner indicating the co-existence of beta 1 and beta 2 sites (30--35% beta 1; 65--70% beta 2) in this tissue. Support for this classification was provided by the binding of the beta 2 agonist procaterol to spleen membranes. This drug possessed high affinity only for those sites that have low affinity for the beta 1 selective agents. Chemical sympathectomy induced by chronic 6-hydroxydopamine administration did not alter the number or the pharmacological properties of beta-adrenoceptor binding sites. The results suggest that both beta 1 and beta 2 adrenoceptors are probably postsynaptic in spleen.

Alprenolol↗
PubMed1985

Beta 1- and beta 2-adrenoceptor binding and functional response in right and left atria of rat heart.

The properties of beta 1- and beta 2-adrenoceptors in right and left atria of rat heart, and their roles in mediating chronotropic and inotropic responses to beta-adrenoceptor agonists were examined. [125I](-)pindolol (125IPIN) bound saturably and specifically to a single class of high affinity sites in homogenates of both right and left atria. The k1's for association in right and left atria were 6.5 X 10(9) l/mol-min and 2.3 X 10(9) l/mol-min respectively, while the k-1's for dissociation were 0.20 min-1 and 0.17 min-1. The kinetically determined KD's were 75 pmol/l in right and 30 pmol/l in left atria and were similar to the equilibrium KD's determined from Scatchard analysis of saturation isotherms of specific 125IPIN binding. Inhibition of 125IPIN binding by beta-adrenoceptor antagonists was stereoselective and the order of potency was timolol greater than l-propranolol greater than d-propranolol greater than sotalol. Inhibition by beta 1- and beta 2-adrenoceptor subtype selective antagonists yielded flat displacement curves with low Hill coefficients. Nonlinear regression analysis of displacement by beta 1-selective (practolol, atenolol and metoprolol) and beta 2-selective (ICI 118,551) antagonists gave estimates of the proportion of beta 1- and beta 2-adrenoceptors present in rat atria. Right atria contained 67 +/- 4.2% beta 1- and 33 +/- 4.2% beta 2-adrenoceptors, while left atria contained 67 +/- 2.8% beta 1- and 33 +/- 2.8% beta 2-adrenoceptors. Increases in the rate of spontaneously beating right atria and the force of electrically driven left atria caused by beta-adrenoceptor agonists were also measured. pA2 values for non-subtype selective beta-adrenoceptor antagonists in inhibiting isoprenaline-induced increases in rate and force were highly correlated with KD values determined for specific 125IPIN binding. pA2 values for beta 1- and beta 2-selective antagonists in inhibiting isoprenaline-induced increases in rate and force correlated well with the pKD values of these drugs in binding to beta 1-adrenoceptors, but not with the pKD values in binding to beta 2-adrenoceptors. Dose-response curves for stimulation of both rate and force by the beta 2-selective agonists procaterol and zinterol were shifted to a much greater extent by selective blockade of beta 1-adrenoceptors with metoprolol than by selective blockade of beta 2-adrenoceptors with ICI 118,551, suggesting that these compounds caused their effects by activating beta 1-adrenoceptors.(ABSTRACT TRUNCATED AT 400 WORDS)

Adrenergic beta-Antagonists↗
PubMed2000

Transforming growth factor-beta1 inhibits beta2-adrenoceptor gene transcription.

Transforming growth factor-beta1 (TGF-beta1) has been shown to modulate beta-adrenoceptor number and function in cultured human tracheal smooth muscle cells and cardiac fibroblasts, but the mechanism is unclear. In this study, we have characterized the beta2-adrenoceptor expression by radioligand binding assay, Northern blot analysis and measurement of intracellular cAMP accumulation in a human embryonic lung fibroblast cell line (HEL299 cells). Treatment with TGF-beta1 caused a time-dependent decrease in beta2-adrenoceptor mRNA, and in receptor number after 24 h. Furthermore, nuclear run-on assays showed a 35% reduction in the transcription rate of the beta2-adrenoceptor gene with no alteration in stability of the beta2-adrenoceptor mRNA. After TGF-beta1 treatment, the basal, procaterol- and forskolin-stimulated cAMP accumulations were also decreased. Cycloheximide inhibited TGF-beta1-mediated reduction of beta2-adrenoceptor mRNA and protein, whilst alone caused induction of beta2-adrenoceptor mRNA without any effect on receptor number. In summary, TGF-beta1 induces beta2-adrenoceptor desensitization through the alteration in adenylyl cyclase activity and down-regulation of beta2-adrenoceptor mRNA and protein through the reduction in the rate of beta2-adrenoceptor gene transcription.

Adrenergic beta-Antagonists↗
PubMed2003

Aerosolized pentamidine prophylaxis against AIDS-related Pneumocystis carinii pneumonia and its short- and long-term effects on pulmonary function in the Japanese.

We evaluated the incidence of prophylaxis failure with aerosolized pentamidine (AP) for Pneumocystis carinii pneumonia (PCP) in Japanese patients with human immunodeficiency virus (HIV) infection, and we examined the short- and long-term effects of AP on pulmonary function. The patients inhaled 300 mg of pentamidine by ultrasonic nebulizer, after the inhalation of procaterol (80 micrograms), every 4 weeks. PCP developed in 2 of 16 patients receiving primary prophylaxis with AP, and in 4 of 13 patients with secondary prophylaxis. The CD4(+) T-lymphocyte count was very low in the patients with prophylaxis failure. The chest radiographic presentations were atypical in 4 of the 6 patients with prophylaxis failure. There were no significant changes in the vital capacity (VC), VC/predictive VC (%VC), forced expiratory volume in 1 s (FEV(1.0)), FEV(1.0)/forced vital capacity (FEV(1.0)%), and maximum expiratory flow rate at 25% of vital capacity (MEF(25))/height comparing values before and after initial AP treatment. However, a reduction of oxygen saturation (SpO(2)) of over 3% was noted in 4 patients during the initial AP administration. In 9 patients receiving AP prophylaxis for more than 36 months, we compared the pulmonary function parameters between the baseline and final observations (mean, 52.7 months). There were no changes in VC, %VC, FEV(1.0,) FEV(1.0)%, and SpO(2), but there was a statistically significant decline in MEF(25)/height after long-term AP treatment. We concluded that the incidence of prophylaxis failure with AP for PCP in Japanese patients was similar to that in Western patients, and that long-term AP treatment affected MEF(25)/height in spite of the safe pulmonary effects in short-term AP inhalation.

AIDS-Related Opportunistic Infections↗
PubMed1983

Adrenergic regulation of glycogenolysis in isolated guinea-pig hepatocytes: evidence that beta 2-receptors mediate catecholamine stimulation of glycogenolysis.

Glycogenolysis in hepatocytes isolated from fed guinea pigs was much more enhanced by the beta-agonist, isoproterenol, than by equimolar concentrations of the alpha-agonists, phenylephrine and norepinephrine. The stimulatory effects of catecholamines occurred with the following order of potency: isoproterenol greater than epinephrine greater than norepinephrine. This order of potency is characteristic of beta 2-adrenergic receptors. That beta 2-receptors are responsible for mediating catecholamine stimulation of glycogenolysis in guinea-pig hepatocytes was further deduced from the inhibition of agonist-stimulated glycogenolysis by beta-receptor sub-type-selective antagonists. Thus, IPS 339, a beta-antagonist which has higher affinity at beta 2-sites than at beta 1-sites, was three orders of magnitude more potent in inhibiting isoproterenol-stimulated glycogenolysis than either atenolol or practolol, both of which are beta 1-selective antagonists. The beta 2-agonists zinterol and procaterol also stimulated glycogenolysis in hepatocytes and their effects were inhibited by propranolol and IPS 339, but not by practolol. Furthermore, activation of phosphorylase in these hepatocytes by isoproterenol, epinephrine, and norepinephrine also occurred with the potency order expected for beta 2-receptors. These results are in sharp contrast to those obtained with rat hepatocytes and emphasize that species differences occur in the regulation of hepatic glycogenolysis by catecholamines.

Animals↗
PubMed1983

Effects of full and partial beta-adrenergic agonists and antagonists on human lung adenylate cyclase.

The beta-adrenergic stimulation of adenylate cyclase in membranes from human lung was compared to that of adenylate cyclase in membranes with a majority of beta 2-adrenergic receptors (from rat lung) and in membranes with a homogeneous population of beta 2-adrenergic receptors (from rat erythrocytes and reticulocytes). In terms of adenylate cyclase stimulation, three full agonists (isoproterenol, epinephrine and norepinephrine), four partial agonists (procaterol, salbutamol, fenoterol and zinterol), and four antagonists (propranolol, metoprolol, atenolol and practolol) were tested. The potency (Kact or Ki) of the eleven beta-adrenergic agents, and the Hill coefficient (of 1) for the four antagonists tested indicated that the activation of human lung adenylate cyclase occurred through receptors of the beta 2-subtype only. Partial beta-adrenergic agonists were efficiently discriminated by the human lung preparation, as shown by distinct intrinsic activities. The mediocre efficacy and the relatively low potency of all beta-adrenergic agonists on adenylate cyclase suggested a relatively low density of beta 2-adrenergic receptors, as compared to the enzyme density.

Adenylyl Cyclase Inhibitors↗
PubMed1982

Specificity of the beta 2-adrenergic receptor stimulating cyclic AMP accumulation in the intermediate lobe of rat pituitary gland.

Changes of cyclic AMP levels were used to assess the specificity of the beta-adrenergic receptor in primary cultures of cells prepared from the intermediate lobe of rat pituitary gland. During a 4 min incubation, beta-adrenergic agonists led to a 4 to 6 fold stimulation of cyclic AMP concentration with the following order of potency (Kd values): zinterol (0.75 nM) greater than hydroxybenzylisoproterenol (1.0 nM) greater than (--)-isoproterenol (4.6 nM) greater than soterenol greater than (7.7 nM) greater than (--)-epinephrine (10 nM) greater than OPC 2009 (procaterol, 11 nM) much greater than (--)-norepinephrine (300 nM). The potent antagonists cyanopindolol, (--)-propranolol and hydroxybenzylpindolol reversed the stimulatory effect of (--)-isoproterenol at Kd values of 0.4-0.6 nM. Other beta-adrenergic antagonists had the following order of potency: pindolol = (--)-alprenolol = timolol (0.9-1.0 mM) much greater than metoprolol (100 nM) greater than dichloroisoproterenol (300 nM) greater than butoxamine (1100 nM). The beta 1-selective antagonist practolol had a low potency at 700 nM. The stereoselectivity of the receptor is indicated by the 400 to 70 fold higher potency of the (--)-isomers of isoproterenol, epinephrine and propranolol as compared to their (+)-stereoisomers. The data show that the beta-adrenergic receptor in the intermediate lobe of the rat pituitary gland is mainly of the bet 2-subtype. Study of this pure population of postsynaptic beta-adrenergic receptors where binding could be correlated with other parameters of cellular activity (cyclic AMP formation and alpha-MSH secretion) should yield useful information about the less accessible adrenergic systems of the brain.

Animals↗
PubMed1983

Beta 2-adrenoceptor-induced hypotension in the ganglion-blocked angiotensin II-supported rat.

An in vivo method is described to demonstrate vascular beta 2-adrenoceptor agonist and antagonist activity. Agonist activity was shown by the ability of i.v. injected compounds to reduce blood pressure in ganglion-blocked, phenoxybenzamine-treated, angiotensin II-supported rats. Procaterol was employed to assess the relative beta 2 blocking activity of propranolol IPS 339 and atenolol. Arunlakshana and Schild analysis of the data revealed that all these compounds were competitively beta 2 antagonists, their relative potencies being 100 : 80 : 0.56 respectively.

Adrenergic beta-Agonists↗
PubMed1987

Behavioural evidence for an interdependence between GABAA receptors and beta 2-adrenoceptors.

The possibility of a functional interdependence between central GABAA receptors and beta 2-adrenoceptors has been investigated using the ability of both types of agonist to potentiate the tic (head-twitch) response to 5-methoxy-N,N-dimethyltryptamine in the mouse. At a dose which selectively antagonised beta 1- but not beta 2-adrenoceptors, ICI 118,551 abolished the effects of single doses of muscimol, diazepam and pentobarbitone. Conversely, bicuculline abolished the potentiation caused by the beta 2-adrenoceptor agonist procaterol. Thus there is preliminary evidence that these two receptor types do show mutual interdependence.

Animals↗
PubMed1995

Myocardial and pulmonary uptake of S-1'-[18F]fluorocarazolol in intact rats reflects radioligand binding to beta-adrenoceptors.

The biodistribution of S-(-)-4-(2-hydroxy-3-(1'-[18F]fluoroisopropyl)- aminopropoxy)carbazole ([18F]S-fluorocarazolol, a non-selective beta-adrenoceptor antagonist) was studied in rats (60 min after 18F injection when specific binding in peripheral organs was maximal). 18F uptake in brain, erythrocytes, heart and lung appeared to be linked to beta-adrenoceptors. CGP-20712A and ICI-89,406 inhibited 18F uptake in heart (predominantly beta 1-adrenoceptors) more potently than in lungs (predominantly beta 2-adrenoceptors). In contrast, ICI-118,551 and procaterol were more potent in the lungs than in the heart. ICI-118,551 inhibited 18F uptake in cerebellum (predominantly beta 2-adrenoceptors) more potently than in cerebral cortex (predominantly beta 1-adrenoceptors). Stereoselectivity of the in vivo binding was demonstrated since S-(-)-propranolol inhibited uptake in target tissues more effectively than R-(+)-propranolol. Myocardial and cerebral imaging may be hampered by poor heart-to-lung contrast and low signal-to-noise ratios, but [18F]S-fluorocarazolol seems suitable for positron emission tomography (PET) of pulmonary beta-adrenoceptors.

Adrenergic beta-Antagonists↗
PubMed1992

Beta 1- and beta 2-adrenoceptors in sheep cardiac ventricular muscle.

The presence of beta 2-adrenoceptors in the sheep ventricular myocardium was assessed by the radioligand binding technique and functional studies. In membrane preparations, the competition curve between [3H]-dihydroalprenolol and the selective beta 1-antagonist CGP 20712A (0.1 nM-1 mM) was clearly biphasic, and revealed the presence of two different binding sites showing an affinity (pKD) for CGP 20712A of 9.5 +/- 0.9 and 4.5 +/- 0.4, respectively. The relative proportion of beta 1:beta 2 adrenoceptors was about 70:30 in both the right and left ventricle. In ventricular trabeculae driven at 1Hz, isoprenaline (1-300 nM) caused a dose-dependent increase in the force of contraction, the maximum effect being 298 +/- 26 mg, associated with reduction of time to peak tension (t1, clinotropic effect) and relaxation time (t2, 298 +/- 26 mg, associated with reduction of time to peak tension (t1, clinotropic effect) and relaxation time (t2, lusitropic effect). The inotropic dose-response curve for isoprenaline was significantly shifted to the right by pretreatment of the preparations with 0.1 microM CGP 20712A or with the selective beta 2-antagonist ICI 118551 (50 nM). In the presence of CGP 20712A (0.1 microM), isoprenaline, up to a concentration of 10 microM, did not affect either t1 or t2; on the other hand, pretreatment of the preparations with ICI 118551 (50 nM) fully antagonized the clinotropic but not the lusitropic effect of isoprenaline. In the presence of CGP 20712A procaterol (0.01-10 microM), a beta 2-adrenoceptor agonist, induced a positive intropic effect which was not associated with any significant modifications in t1 or t2. This effect was completely abolished by ICI 118551 (50 nM). The positive inotropic action of isoprenaline (1 microM) was associated with a significant decrease in action potential duration measured at -60 mV (220 +/- 8 and 193 +/- 10 ms in the absence and presence of isoprenaline, respectively; P less than 0.05). In the presence of CGP 20712A (0.1 microM) alone, isoprenaline (1 microM) still induced a significant increase in contractility but the action potential profile was only slightly affected. The effects of isoprenaline were fully antagonized by the simultaneous presence of CGP 20712A and ICI 118551 (10 nM). It is concluded that both beta 1- and beta 2-adrenoceptors appear to coexist in sheep ventricular myocardium where their stimulation mediates a positive inotropic effect. However, their functional role on the relaxation phase of the twitch may be different.

Action Potentials↗
PubMed1986

Involvement of the locus coeruleus in the potentiation of the quipazine-induced head-twitch response by diazepam and beta-adrenoceptor agonists.

Head-twitching in rats induced by quipazine was reduced by bilateral lesions of the locus coeruleus (LC) produced by 6-hydroxydopamine. Both beta 1-and beta 2-adrenoceptor agonists potentiated the head-twitch induced by quipazine in sham-operated controls. Lesions of the locus coeruleus increased the responses to the beta 1-adrenoceptor agonists, prenalterol and dobutamine, but reduced the response to the beta 2-adrenoceptor agonists, salbutamol and procaterol. Diazepam (0.25 mg/kg) also potentiated the response to quipazine and this was reversed to inhibition by lesions of the locus coeruleus. These results suggest that the beta 1-adrenoceptors involved are postsynaptic and the beta 2-adrenoceptors are presynaptic to neurones of the locus coeruleus and indicate a dual action of diazepam on the head-twitch induced by quipazine. Possible mechanisms for these effects are discussed.

Adrenergic beta-Agonists↗
PubMed1985

Correlation between agonist potency, desensitization and internalization of beta adrenergic receptors in a muscle cell line.

The mechanism(s) of agonist-induced desensitization of the beta adrenergic receptor-coupled adenylate cyclase has been investigated in the L8 skeletal muscle cell line. Different beta agonists stimulate cAMP accumulation in intact L8 cells with the following potency: Isoproterenol greater than Procaterol = Epinephrine greater than Norepinephrine greater than Phenylephrine. Preincubation of intact cells for 30 min at 37 degrees C with the same agonists induces a dose-dependent desensitization of beta receptor function. The degree of desensitization induced is correlated with the potency of agonists in stimulating cAMP accumulation. The same agonists induced internalization of the adrenergic beta receptor, with potency similar to that inducing desensitization and cAMP accumulation. Thus it is possible to conclude that in L8 cells beta receptor are of the beta 2 subtype and that agonist-induced beta adrenergic receptor desensitization proceeds via internalization of the beta adrenergic recognition site.

Adrenergic beta-Agonists↗
PubMed2006

Protein kinase C attenuates beta-adrenergic receptor-mediated lipolysis, probably through inhibition of the beta1-adrenergic receptor system.

Lipolysis in rat white adipocytes is stimulated by beta-adrenergic agonists. Phorbol 12-myristate 13-acetate (PMA) attenuated the receptor-mediated lipolysis by causing a shift of the dose-response curve to the higher concentrations of norepinephrine and isoproterenol. Although the adipocytes possess beta1-, beta2-, and beta3-adrenergic receptor subtypes, the effect of PMA was observed only when a beta1-agonist (dobutamine) was used. No lipolysis-attenuating effect of PMA was found when cells were exposed to a beta2-agonist (procaterol) and beta3-agonists (BRL 37344 and CL 316243), or to forskolin and 8-bromo cAMP. CGP 20712A (beta1-antagonist) efficiently inhibited lipolysis by norepinephrine, isoproterenol, and dobutamine, but did not affect lipolysis by the beta2- and beta3-agonists. ICI 118551 (beta2-antagonist) had no significant effect on lipolysis by the beta-agonists examined. CGP 20712A abolished the lipolysis-attenuating effect of PMA, but ICI 118551 did not. The protein kinase C (PKC) inhibitors, GF 109203X or Gö 6976, suppressed the effect of PMA. Pretreatment of adipocytes with PMA for 6 h caused downregulation of conventional and novel PKCs in association with a decrease in the lipolysis-attenuating effect of PMA. These results indicate that conventional and novel PKCs attenuate lipolysis mediated by beta-adrenergic receptors, probably through inhibition of the beta1-adrenergic receptor system.

Adipocytes↗