Species and strain-related differences in the expression and functionality of beta-adrenoceptor subtypes in adipose...

The beta-adrenoceptor subtypes which trigger lipolysis in white adipocytes vary markedly between calf and rats, and even between different rat strains. In calf adipocytes, CGP12177, a potent antagonist for beta 1- and beta 2-adrenoceptors (i.e., "classical beta-adrenoceptors") and a partial agonist for atypical beta-adrenoceptors, did not stimulate lipolysis, but inhibited with high affinity (IC50 = 0.66 nM) the lipolytic response to 10 nM isoproterenol. In adipocytes from both Wistar rats and Sprague-Dawley OFA rats, CGP12177 stimulated lipolysis to almost the same extent as isoproterenol. Low concentrations of CGP12177 (3 nM) inhibited part of the lipolytic response to 10 nM isoproterenol in the Sprague-Dawley OFA rat adipocytes, but not in Wistar rats at all ages tested (2-4 weeks, 2-4 months, 24-26 months). Hence, functional beta-adrenoceptors are only classical in calf adipocytes, only atypical in Wistar rat adipocytes and both classical and atypical in Sprague-Dawley OFA rat adipocytes. Binding experiments were performed with 150 pM [125I]CYP. On calf adipocyte membranes, competition binding curves with CGP12177 displayed one high affinity binding site (IC50 = 4.7 nM), whereas the curves for CGP20712 (beta 1-selective antagonist) and ICI118551 (beta 2-selective antagonist) were biphasic. In agreement with the functional data, these results indicate that only beta 1- and beta 2-adrenoceptors are present in calf adipose tissue. For both rat strains, only half of the displaceable [125I]CYP binding sites displayed high affinity for CGP12177 (IC50 = 6.8 to 7.5 nM), and competition binding studies with CGP20712 and ICI118551 indicated that they represent beta 1- and beta 2-adrenoceptors. The remaining [125I]CYP binding sites possessed an about 50 times lower affinity for CGP12177 (IC50 = 260 to 345 nM). They are likely to represent atypical beta-adrenoceptors. It is concluded that the presence and the physiological relevance of beta-adrenoceptor subtypes in adipose tissue may not only be species-related, but also strain-related.