Muscarinic receptor interaction with full and partial beta-adrenoceptor agonists in the rat colon strip.
beta-Adrenoceptor agonists inhibit contractile activity in isolated colon strips. In order to demonstrate that beta-adrenoceptors are located at different functional levels within the colon wall, increasing concentrations of muscarinic agonists were used to interact functionally with the beta-adrenoceptor-mediated inhibition of spontaneous colon activity. The effects of the full agonists isoprenaline and terbutaline and of the partial agonist prenalterol were functionally antagonized by carbachol (0.03 and 0.3 mumol/l) and bethanechol (1.3 and 30 mumol/l). This functional antagonism was parallelled by an increase in baseline tension and spontaneous contractile activity of the isolated colon strip. At lower concentrations of carbachol (0.003 and 0.01 mumol/l) or bethanechol (0.03 and 0.3 mumol/l) no effect on the contractile status of the smooth muscle or on the pD2-values of the full agonists was seen. However, at these lower concentrations of muscarinic agonists a marked decrease in the maximal inhibitory response to the partial beta-adrenoceptor agonist prenalterol was demonstrated. The inhibitory response to prenalterol showed a biphasic concentration-response curve. The muscarinic antagonist atropine produced an increase in the maximal response of the high potency component of the concentration-response curve for prenalterol and an increase in the sensitivity to isoprenaline. These results demonstrate the presence of a high cholinergic tone in the colon preparation of a magnitude that clearly reduces the sensitivity to beta-adrenoceptor agonists. The different responses to full and partial beta-adrenoceptor agonists in the presence of increasing concentrations of muscarinic agonists may indicate that beta-adrenoceptors are located on two different functional units within the colon wall.
D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000818:Animals; D001626:Bethanechol Compounds / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology; D003106:Colon / Q000187:drug effects / Q000502:physiology; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D011294:Prenalterol / Q000494:pharmacology; D051381:Rats; D011976:Receptors, Muscarinic / Q000187:drug effects / Q000502:physiology*; D013726:Terbutaline / Q000494:pharmacology
D000318:Adrenergic beta-Agonists; D001626:Bethanechol Compounds; D011976:Receptors, Muscarinic; D002217:Carbachol; D007545:Isoproterenol; D011294:Prenalterol; D013726:Terbutaline