INCREASED ACTIVE STRESS GENERATION OF DENERVATED RAT INTESTINAL SMOOTH-MUSCLE - FUNCTIONAL-ANALYSIS OF MUSCARINIC RECEPTOR POPULATION

The effects of denervation on the active stress production by the long itudinal muscle (LM) layer of rat jejunum were examined. Extrinsic and myenteric denervation of a segment of rat jejunum was accomplished by the serosal application of the cationic surfactant benzyldimethyltetr adecylammonium chloride (BAC). Isolated muscle contraction experiments revealed that the LM of the jejunum taken from rats treated with BAC 15 days before developed significantly increased active stress in resp onse to bethanechol and carbachol, but not in response to potassium ch loride. No change in -log EC(50) values of any of the agonists was obs erved in the denervated LM layer, although a significant increase in t he slope of the carbachol and bethanechol concentration-response curve s was observed in the denervated LM. Schild analysis of several muscar inic antagonists revealed a 3-fold increase in the apparent dissociati on constant of the M(2) antagonist methoctramine in BAC-treated LM. Th ese results suggest that the increased responsiveness of the denervate d LM may originate in the muscarinic receptor population of the myocyt es.