Expression and activation of β-adrenoceptors in the colorectal mucosa of rat and human

Background The functions of the distal colon are regulated by local and extrinsic neural pathways. In previous studies, we have found that dopamine (DA) and norepinephrine (NE) could evoke colonic ion transport by activating beta-adrenoceptors. The present study aims to investigate the segmental differences in expression and activation of beta-adrenoceptors in the distal colon in physiological and pathophysiological conditions. Methods Real-time PCR, immunofluorescence, and Western blotting were used to detect the expression of beta-adrenoceptors in the rat and human distal colon. Short-circuit current measurements (I-sc) were used to assess the role of beta-adrenoceptors in ion transport. Key Results DA and NE caused greater suppression of baseline I-sc in distal colon adjacent to the rectum than in segments further away from the anus. These responses were inhibited by selective antagonists of beta(1)- and beta(2)-adrenoceptors, but not beta(3)-adrenoceptor. The expression levels of beta(1)- and beta(2)-adrenoceptors in colonic mucosa were higher in colorectum than the regions away from the anus of rats and humans. In wrap-restraint stress (2 h), DA-, NE-induced Delta I-sc and the expression of beta-adrenoceptors in the colorectum were significantly reduced. However, when endogenous catecholamines were depleted by 6-hydroxydopamine (75 mg kg-1, i.p., 3 days), DA-, NE-induced Delta I-sc as well as the expression of beta-adrenoceptors were significantly enhanced in the rat colorectum but not in more proximal regions of the distal colon. Conclusions & Inferences beta(1)- and beta(2)-adrenoceptors are predominantly expressed in the colorectal mucosa. Perturbation of endogenous catecholamine levels influences the expression and activation of beta-adrenoceptors in the colorectal region.