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Journal of Pharmacology And Experimental Therapeutics Fast Forward
First published on October 20, 2003; DOI: 10.1124/jpet.103.057612

0022-3565/04/3081-241-248$20.00
JPET 308:241-248, 2004
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GASTROINTESTINAL, HEPATIC, PULMONARY, AND RENAL

The Inhibitory Effect of Adrenomedullin in the Rat Ileum: Cross-Talk with {beta}3-Adrenoceptor in the Serotonin-Induced Muscle Contraction

Gennadi M. Kravtsov, Isabel S. S. Hwang, and Fai Tang

Department of Physiology, Faculty of Medicine, University of Hong Kong, Hong Kong, China

In contrast to vascular muscles, the contribution of a hypotensive peptide adrenomedullin (AM) to the regulation of visceral smooth muscles is obscure. The content, synthesis, and effects of AM on the muscular tone in rat ileum were explored. It was found that there was immunoreactive AM (301 pg/mg of protein) and AM mRNA expression (162 fg/pg actin mRNA) in the ileum and that AM evoked relaxation in ileal strips (Ki = 0.85 nM) precontracted with serotonin. Antagonists of both AM (AM22-52) and calcitonin gene-related peptide (CGRP8-37) receptors did not affect this AM-induced relaxation, whereas it was suppressed by a selective blocker of {beta}3-adrenoreceptor (SR 59230A). The AM-induced relaxation was accompanied by a production of cAMP. Antagonists of protein kinases A (KT 5720 and H-7) and an inhibitor of the ATP-dependent K+-channels (glibenclamide) attenuated the effect of AM. We suggest that AM is a local regulator of the ileal tone, with an inhibitory action on muscle contraction. AM may activate the {beta}3-adrenoceptors, resulting in protein kinase A activation, which in turn opens the ATP-dependent K+-channels.

Received July 25, 2003; accepted October 8, 2003.

Address correspondence to: Dr. G. M. Kravtsov, Department of Physiology, The University of Hong Kong, 4/F Laboratory Block, Faculty of Medicine Building, 21 Sassoon Road, Hong Kong, China. Email: gmkravts{at}hkucc.hku.hk




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