In vitro inhibition of intestinal motility by phenylethanolaminotetralines: evidence of atypical β‐adrenoceptors in rat colon

Abstract

1 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 × 10⁻⁵ m.) on the guinea-pig isolated atrium (a β₁-adrenoceptor-mediated response). 2 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). 3 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. 4 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.