Increased beta I-adrenoceptor density after 6-hydroxydopamine pretreatment in rat colon and lung

Abstract

Estimation of beta-adrenoceptor-binding sites with 125I-(-)-pindolol in rat colon show a proportion of 30% beta I-adrenoceptors and 70% beta 2-adrenoceptors. Studies on the isolated colon strip have revealed a neuronal beta-adrenoceptor involved in the inhibitory response of colon motility to beta-adrenoceptor stimulation. In order to further characterize the beta-adrenoceptors in the colon, acute and chronic treatments with 6-hydroxydopamine were made. Both acute pretreatment of rats with 6-hydroxydopamine for 8 and 24 h (one intravenous injection) and chronic treatment for 3 days (implanted osmotic mini-pumps), reduced the noradrenaline tissue content by 90%, and successively increased the beta-adrenoceptor-binding sites from 14.2 to 21.7 fmol mg-I P-I in colon and from 158 to 240 fmol mg-I P-I in lung membranes. Displacement of the radiolabelled ligand by the selective beta-adrenoceptor antagonists, pafenolol and ICI 118.551 showed that the density of beta I-adrenoceptor binding sites was more than doubled, whereas the density of beta 2-adrenoceptor-binding sites was only marginally increased by chronic treatment with 6-hydroxydopamine. Thus sympathetic denervation by 6-hydroxydopamine treatment produced a selective increase in beta I-adrenoceptors in the rat colon. These results may indicate that stimulation of beta I-adrenoceptors in both colon and lung have a neuronal linkage.