INVITRO INHIBITION OF INTESTINAL MOTILITY BY PHENYLETHANOLAMINOTETRALINES - EVIDENCE OF ATYPICAL BETA-ADRENOCEPTORS IN RAT COLON

The new compounds phenylethanolaminotetralines (PEAT), unlike the reference β-adrenoceptor agonists isoprenaline (Iso), ritodrine (Ri) and salbutamol (Sal), produced half-maximal inhibition of spontaneous motility of rat isolated proximal colon at substantially lower concentrations (EC50 2.7 - 30 nM) than those inducing β2-adrenoceptor-mediated responses (relaxation of guinea-pig isolated trachea and rat uterus) and had virtually no chronotropic action (EC50 > 3 x 10-5M) on the guinea-pig isolated atrium (a β1-adrenoceptor-mediated response). The nonselective β-adrenoceptor antagonists alprenolol and propranolol prevented the inhibition of rat colon motility by the PEAT with low and different potencies (pA2 values around 7.5 and 6.5 respectively). Conversely alprenolol and propranolol had a higher and similar potency (pA2 values around 9.0) in preventing typical β1- or β2-responses (increase in atrial frequency by Iso or tracheal relaxation by Ri or Sal). The selective β-adrenoceptor antagonists (CGP 20712A (β1) and ICI 118,551 (β2) either alone or in combination, did not prevent rat colon motility inhibition by the representative PEAT SR 58611A, which was also fully resistant to α-adrenoceptor, acetylcholine, dopamine, histamine, opioid and 5-hydroxytryptamine antagonists. These results indicate that the PEAT are a new class of β-adrenoceptor agonists and suggest that their preferential intestinal action may be accounted for by selectivity for atypical β-adrenoceptors, abundant in the rat colon and distinct from the currently recognized β1 and β2 subtypes.