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 beta3-adrenoceptor antagonist cyanopindolol. The beta3-adrenoceptor agonist CL216343 elicited concentration-dependent relaxation of the muscularis mucosae in all regions of the colon. Isoprenaline, a non-selective beta-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 alpha1-adrenoceptor agonist methoxamine caused large contractions of the proximal colonic muscularis mucosae. When proximal tissue was pretreated with phentolamine, an alpha1-adrenoceptor antagonist, maximal noradrenaline- and isoprenaline-induced relaxations did not differ significantly. Although the mid colonic muscularis mucosae was also found to possess excitatory alpha1-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 beta3-adrenoceptor-mediated relaxations. No evidence was obtained for functional alpha2-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 beta3-adrenoceptors throughout, but in the proximal region this was modified by concurrent excitatory alpha1-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.
Percy
William H
WH
Division of Basic Biomedical Sciences, Sanford School of Medicine, The University of South Dakota, Vermillion, SD 57069-2390, USA. wpercy@usd.edu
Keupp
Sarah M
SM
D000322:Adrenergic Agonists / Q000494:pharmacology*; D018674:Adrenergic Antagonists / Q000494:pharmacology*; D000818:Animals; D003106:Colon / Q000187:drug effects* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects* / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011941:Receptors, Adrenergic / Q000187:drug effects* / Q000378:metabolism; D018340:Receptors, Adrenergic, alpha-1 / Q000187:drug effects / Q000378:metabolism; D022702:Receptors, Adrenergic, beta-3 / Q000187:drug effects / Q000378:metabolism
D000322:Adrenergic Agonists; D018674:Adrenergic Antagonists; D011941:Receptors, Adrenergic; D018340:Receptors, Adrenergic, alpha-1; D022702:Receptors, Adrenergic, beta-3; D009638:Norepinephrine