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Adrenergic responses of rat colonic muscularis mucosae

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.