Title: Modulation of airway smooth muscle beta-adrenoceptor function by a muscarinic agonist Grandordy BM, Mak JC, Barnes PJ Ref: Life Sciences, 54:185, 1994 : PubMed
We have investigated the effect of a muscarinic agonist and protein kinase C (PKC) activation on beta-adrenoceptors and their coupling to adenylyl cyclase in bovine tracheal smooth muscle. There was a significant reduction in maximum binding capacity of [125I]iodocyanopindolol ([125I]ICYP) after exposure to carbachol and 4 beta-phorbol 12 beta-myristate 13 alpha-acetate (PMA). Similarly both carbachol and PMA inhibited the 5'-guanylylimidodiphosphate-induced shift in [125I]ICYP binding by isoproterenol and significantly decreased isoproterenol-induced cyclic AMP accumulation. A phorbol ester, 4 alpha-phorbol 12,13-didecanoate which does not activate PKC had no effect on beta-receptor binding or coupling. These results suggest that PKC activation directly via a phorbol ester and indirectly via muscarinic receptor stimulation may lead to reduction and uncoupling of beta-receptors in airway smooth muscle. We suggest that this mechanism may be relevant to the reduction in beta-receptor coupling in asthmatic airways as an effect of PKC activation by inflammatory mediators and neurotransmitters.
        
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Grandordy BM, Mak JC, Barnes PJ (1994) Modulation of airway smooth muscle beta-adrenoceptor function by a muscarinic agonist Life Sciences54: 185-91
Grandordy BM, Mak JC, Barnes PJ (1994) Life Sciences54: 185-91