Increased β1-adrenoceptor density after 6-hydroxydopamine pretreatment in rat colon and lung

Estimation of β-adrenoceptor-binding sites with ¹²⁵I-(-)-pindolol in rat colon show a proportion of 30%β₁,-adrenoceptors and 70%β₂-adrenoceptors. Studies on the isolated colon strip have revealed a neuronal β-adrenoceptor involved in the inhibitory response of colon motility to β-adrenoceptor stimulation. In order to further characterize the β-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 β-adrenoceptor-binding sites from 14.3 to 21.7 fmol mg^_1 P^_1 in colon and from 158 to 240 fmol mg^-1 P^_1 in lung membranes. Displacement of the radiolabelled ligand by the selective β-adrenoceptor antagonists, pafenolol and ICI 118.551 showed that the density of β₁,-adrenoceptor binding sites was more than doubled, whereas the density of β₂-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 β₁-adrenoceptors in the rat colon. These results may indicate that stimulation of β₁-adrenoceptors in both colon and lung have a neuronal linkage.