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Authors: Percy, William H.¹; Keupp, Sarah M.²

Source: Journal of Pharmacy and Pharmacology, Volume 60, Number 8, August 2008 , pp. 1097-1103(7)

Abstract:

We have investigated adrenoceptor-mediated responses of muscularis mucosae from the proximal, mid and distal regions of the rat colon. Noradrenaline-induced relaxations of the muscularis mucosae in each region were unaffected by atenolol, butoxamine or propranolol, but they were attenuated by the selective β₃-adrenoceptor antagonist cyanopindolol. The β₃-adrenoceptor agonist CL216343 elicited concentration-dependent relaxation of the muscularis mucosae in all regions of the colon. Isoprenaline, a non-selective β-adrenoceptor agonist, evoked concentration-dependent relaxations of the muscularis mucosae in all regions, but only in the proximal colon were these significantly larger than the maximum noradrenaline-induced relaxation. The α₁-adrenoceptor agonist methoxamine caused large contractions of the proximal colonic muscularis mucosae. When proximal tissue was pretreated with phentolamine, an α₁-adrenoceptor antagonist, maximal noradrenaline- and isoprenaline-induced relaxations did not differ significantly. Although the mid colonic muscularis mucosae was also found to possess excitatory α₁-adrenoceptors, these were associated with small contractions and did not modify the muscle's inhibitory responses to noradrenaline. Distal colonic muscularis mucosae lacked excitatory adrenoceptors and only responded to noradrenaline with β₃-adrenoceptor-mediated relaxations. No evidence was obtained for functional α₂-adrenoceptors on the muscularis mucosae in any region of the rat colon. These data demonstrated that noradrenaline-induced relaxation of the rat colonic muscularis mucosae was mediated via β₃-adrenoceptors throughout, but in the proximal region this was modified by concurrent excitatory α₁-adrenoceptor activation. Based upon these observations it appeared unlikely that noradrenaline-induced relaxation of rat colonic muscularis mucosae would be functionally linked to the secretory responses of the corresponding mucosa during periods of increased sympathetic activity.

Document Type: Review article

DOI: 10.1211/jpp.60.8.0016

Affiliations: 1: Division of Basic Biomedical Sciences, Sanford School of Medicine, The University of South Dakota, Vermillion, SD 57069-2390, USA., Email: wpercy@usd.edu 2: Division of Basic Biomedical Sciences, Sanford School of Medicine, The University of South Dakota, Vermillion, SD 57069-2390, USA

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