Inhibition of rat colon motility by stimulation of atypical beta-adrenoceptors with new gut-specific agents

Summary The new putative beta-adrenergic agonists SR 58306A, 2-[(7-hydroxy-1,2,3,4-tetrahydronaphth-2-yl)amino]-1-phenylethanol hydrochloride and SR 58339A, 2-[(7-hydroxy-1,2,3,4-tetrahydronaphth-2-yl)amino]-1-(3-chlorphenyl) ethanol hydrochloride, were studied in vitro in comparison with reference compounds. SR 58306A and SR 58339A, unlike isoprenaline and the beta 2 selective adrenergic agonists salbutamol and ritodrine, potently inhibited rat colon spontaneous contractions (EC 50 5.9 and 1.1×10 −7 M) without increasing guinea-pig atrium frequency or relaxing guinea-pig trachea. The non-selective beta-adrenergic antagonists alprenolol, pindolol and propranolol competitively antagonized the action of SR 58306A on the colon, which was not prevented by either of the selective antagonists atenolol (beta 1 ) and ICI 118551 (beta 2 ). In the same preparation only alprenolol competitively antagonized isoprenaline; antagonism by either pindolol or propranolol was not competitive. These results suggest that in the rat colon isoprenaline interacts with different beta-receptor subclasses, whereas our new gut-specific compounds such as SR 58306A inhibit colonic motility by selectively stimulating atypical beta-adrenoceptors.