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Both beta-1 and beta-2 adrenoceptors are coupled to the cyclic AMP system in connecting tubules of rabbit nephron.

The connecting tubule (CNT), a segment interposed between distal convoluted tubules and collecting ducts, is a well defined segment in the rabbit nephron and have been shown to contain adenylate cyclase activity which is responsive to the beta agonist isoproterenol (ISO) and the nonselective beta blocker propranolol. We examined whether ISO also increased cAMP levels in the intact microdissected CNT in the presence of 1-methyl-3-isobutyl-xanthine and, in particular, which subtype of beta adrenoceptors was stimulated. ISO increased cAMP contents in a dose-dependent way (ED50 approximately equal to 10(-7) M) and the maximal stimulation was achieved at 1 microM ISO. Norepinephrine also elevated cAMP content in the CNT to the same extent as ISO. The increase in cAMP stimulated by ISO and norepinephrine was inhibited by 1 microM propranolol but not by 1 microM phenoxybenzamine. ISO-induced cAMP increased was blocked by the beta-1 antagonist metoprolol and also by the beta-2 antagonist ICI-118551 independently in a dose-dependent manner, and maximal inhibition was observed at 1 microM of both antagonists. These results indicate that both beta-1 and beta-2adrenoceptors appear to be located in the rabbit CNT and both can be positively coupled to adenylate cyclase to generate cAMP accumulation.