β-adrenoceptor studoes. III On the β-adrenoceptors in rat adipose tissue

Harms, Herman H.; Zaagsma, Johan; Wal, B. van der

doi:10.1016/0014-2999(74)90098-3

Cited by 71 publications

(30 citation statements)

References 6 publications

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“…An atypical or hybrid f-adrenoceptor was already suggested by Harms et al (1974) and by De Vente et al (1980), who demonstrated low affinity of this adrenoceptor for both ff1-and 42-selective and non-selective antagonists. In addition, for the adipocyte fiadrenoceptor atypically low stereoselectivity ratios of antagonist enantiomers were found compared to typical fi1- (cardiac) and f2-(skeletal muscle) adrenoceptors (Harms et al, 1977).…”

Section: Introductionmentioning

confidence: 74%

Relationship between lipolysis and cyclic AMP generation mediated by atypical β‐adrenoceptors in rat adipocytes

Hollenga

Brouwer

Zaagsma

1991

British J Pharmacology

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1 The nature of the fi-adrenoceptor(s) mediating adenylyl cyclase activation in rat adipocyte ghosts by (-)-isoprenaline and the lipolytically selective fi-adrenoceptor agonist, BRL 37344, was investigated by use of the fli-selective antagonist, CGP 20712A. The results were compared with lipolysis in adipocytes.2 While in lipolysis BRL 37344 was a full and 10 times more potent agonist than (-)-isoprenaline, in adenylyl cyclase activation similar pD2 values for both agonists were found. BRL 37344 was only a partial agonist on rat adipocyte adenylyl cyclase, with an intrinsic activity of 0.62. 3 With CGP 20712A small rightward shifts of the (-)-isoprenaline concentration-response curve (CRC) were observed at concentrations up to 10pM, while at 100pM and 1 mm clear rightward shifts occurred. The BRL 37344 CRC was not shifted with antagonist concentrations up to 10pM. Only at 100pM and 1mM CGP 20712A were rightward shifts observed.4 CGP 20712A concentrations of 1OpM and 100pM depressed the maximum of the (-)-isoprenaline CRC to 89 and 60%, while the BRL 37344 CRCs retained the control maximum effect (62% of (-)-isoprenaline). Only at 1 mm CGP 20712A, was the CRC of BRL 37344 depressed, while the (-)-isoprenaline maximum was diminished further. 5It was concluded that as with lipolysis, (-)-isoprenaline acts both through typical f1-and atypical 63-adrenoceptors for activation of adenylyl cyclase, while BRL 37344 acts solely through atypical f3-adrenoceptors.6 The results also demonstrate that the relationship between adenosine 3':5'-cyclic monophosphate (cyclic AMP) and lipolysis is different for BRL 37344 and (-)-isoprenaline. Although the maximum activation of adenylyl cyclase by BRL 37344 is only 62% of that by (-)-isoprenaline, the distance between the lipolysis and adenylyl cyclase CRCs is much larger in the case of BRL 37344, indicating a larger transduction reserve for this agonist.

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Section: Introductionmentioning

confidence: 74%

Relationship between lipolysis and cyclic AMP generation mediated by atypical β‐adrenoceptors in rat adipocytes

Hollenga

Brouwer

Zaagsma

1991

British J Pharmacology

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“…heart and adipose tissue as fil. However, a considerable number of reports indicate that there are differences between the pharmacological characteristics of cardiac and adipose tissue fiadrenoceptors, both in animals and in man (Harms, Zaagsma & van der Wal, 1974;Goldberg, Joffe, Bersohn, Van As, Krut & Seftel, 1975;Gibbons et al, 1975;Harms, 1976b). Comparison of the antagonist potencies of several cardioselective P-adrenoceptor blocking agents on human cardiac, bronchial and adipocyte fl-adrenoceptors against isoprenaline induced effects (Harms & van der Meer, 1975;Harms, 1976a) also suggests that these agents are somewhat less effective in blocking adipocyte fl-adrenoceptors than cardiac,B-adrenoceptors.…”

Section: Plasma Renin Activitymentioning

confidence: 99%

Blockade of isoprenaline‐induced changes in plasma free fatty acids, immunoreactive insulin levels and plasma renin activity in healthy human subjects, by propranolol, pindolol, practolol, atenolol, metoprolol and acebutolol.

Harms¹,

Gooren²,

Spoelstra³

et al. 1978

Brit J Clinical Pharma

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I The effects of intravenously administered propranolol 0.01 and 0.03, pindolol 0.001 and 0.003, practolol 0.12 and 0.36, atenolol 0.03 and 0.09, metoprolol 0.045 and 0.135 and acebutolol 0.12 and 0.36 mg/kg, on isoprenaline-induced changes in heart rate, blood pressure, plasma free fatty acids, immunoreactive insulin plasma levels and plasma renin activity were determined in six healthy human subjects. 2 Propranolol, atenolol and metoprolol had a stronger effect on resting heart rate than practolol, acebutolol and pindolol, probably reflecting differences in intrinsic f,-sympathomimetic activity.Antagonist potencies against isoprenaline-induced changes in heart rate and blood pressure suggested cardioselectivity for practolol, atenolol, metoprolol and the lower dose of acebutolol and noncardioselectivity for propranolol, pindolol and the higher dose of acebutolol. 3 All six f-adrenoceptor blocking agents were able, to a varying extent, to antagonize the isoprenaline-induced increases in plasma free fatty acids and plasma immunoreactive insulin levels. In general, the cardioselective agents were relatively less effective antagonists than the non-cardioselective agents.4 Resting plasma renin activity was reduced by all six fJ-adrenoceptor blocking agents, suggestive of the presence of fJ1-adrenoceptors mediating renin release, but the non-cardioselective agents propranolol and pindolol seemed relatively more effective in antagonizing isoprenaline-induced increases in plasma renin activity than the cardioselective agents, which indicates that 62-adrenoceptors might also be involved.5 The results are compatible with the hypothesis that both #,-and fJ2-adrenoceptors are involved in the regulation oflipolysis, insulin release and renin release.

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“…This was found not only in lipolysis experiments, but also with cyclic AMPaccumulation in intact cells and adenylyl cyclase in adipocyte membranes (Bojanic et al, 1985). The early suggestion of a hybrid nature of the adipocyte f-adrenoceptor (Harms et al, 1974) and references cited therein). In addition, it was established that the atypical behaviour of antagonists was not due to a heterogeneous population of both i1-and fi2-adrenoceptors (De Vente et al, 1980;Bojanic et al, 1985).…”

Section: Methodsmentioning

confidence: 99%

Direct evidence for the atypical nature of functional β‐adrenoceptors in rat adipocytes

Hollenga

Zaagsma

1989

British J Pharmacology

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103

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1 The nature of the rat epididymal adipocyte ,B-adrenoceptor was investigated by studying the effects of #,-and f2-selective antagonists on lipolysis induced by (-)-isoprenaline and the lipolytically selective agonist BRL 37344.2 From lOnM to 10pM, the potent and highly selective fI-adrenoceptor antagonist CGP 20712A did not influence the concentration-response curve (CRC) of BRL 37344 whereas small but consistent shifts to the right of the (-)-isoprenaline-induced CRC were observed. Clear rightward shifts of the CRCs induced by both (-)-isoprenaline and BRL 37344 were produced only at 100pM CGP 20712A with the corresponding pA2 values being 4.80 and 4.61, respectively.3 When the #2-selective antagonist ICI 118,551 was used at 10 pM and higher, clear and concentration-dependent shifts to the right of the CRCs of both agonists were observed. The slopes of the Schild plots did not deviate significantly from unity, the pA2 values being 5.49 and 5.33 against (-)-isoprenaline and BRL 37344, respectively. 4 The results demonstrate that (-)-isoprenaline-induced lipolysis in rat white adipocytes is mediated predominantly by atypical f-adrenoceptors, whereas the typical fl-adrenoceptors play a small, subordinate role. The lipolytically selective agonist BRL 37344 acts solely through atypical fiadrenoceptors.

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β-adrenoceptor studoes. III On the β-adrenoceptors in rat adipose tissue

Cited by 71 publications

References 6 publications

Relationship between lipolysis and cyclic AMP generation mediated by atypical β‐adrenoceptors in rat adipocytes

Relationship between lipolysis and cyclic AMP generation mediated by atypical β‐adrenoceptors in rat adipocytes

Blockade of isoprenaline‐induced changes in plasma free fatty acids, immunoreactive insulin levels and plasma renin activity in healthy human subjects, by propranolol, pindolol, practolol, atenolol, metoprolol and acebutolol.

Direct evidence for the atypical nature of functional β‐adrenoceptors in rat adipocytes

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