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.

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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