Functional effects of beta(3)-adrenoceptor on pacemaker activity in interstitial cells of Cajal from the mouse colon

摘要

We investigated the presence of beta(3)-adrenoceptor and its functional effects on pacemaker potentials in colonic interstitial cells of Cajal (ICCs) from mice. The whole cell patch clamp technique was used to record pacemaker potentials in cultured ICCs and reverse transcription polymerase chain reaction (RT-PCR) was performed to detect the mRNA transcript levels beta-adrenoceptors. The beta(3)-adrenoceptor agonist, BRL37344, reduced the frequency of pacemaker potentials in a Concentration dependent manner. The inhibitory effects of BRL37344 wore blocked by the pretreatment of propranolol, a nonspecific beta-adrenoceptor antagonist, but not by the selective beta(1)-adrenoceptor antagonist atenolol and the selective beta(2)-adrenoceptor antagonist butoxamine. beta(3)-adrenocepto antagonists SR59230A and L748337 blocked the inhibitory effects of BRL37344. RT-PCR revealed mRNA transcripts of beta(1)- and beta(3)-adrenoceptor, but not beta(2)-adrenoceptor, in c-kit- and Ano-1-positive colonic ICCs. The K+ channel blockers tetraethylammoniu, apamin, and glibenclamide did not block the effects of BRL37344. N-omega-Nitio-L-arginiue methyl ester hydrochloride (L-NAME), an NO synthase inhibitor, and chelerythrine, a protein Kinase C inhibitor, also did not block the effects of BRL37344. Noradrenaline mimicked the effects of BRL37344 in colonic ICCs. However, the inhibitory effects of noradrenaline on pacemaker potentials were blocked only by pretreatment with atenolol but not by butoxamine, SR59230A, or L748337 in small intestinal ICCs, BRL37344 had no effect On pacemaker potentials and mRNA transcripts of beta(1)-and beta(2)-adrenoceptor, but not beta(3)-adrenoceptor were detected. These results suggest that beta(3)-adrenoceptors are present in colonic ICCs and may play a role in regulating gastrointestinal motility by the inhibition or pacemaker potentials. (C) 2015 Elsevier By. All rights reserved.