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 β-adrenoceptors. The present study aims to investigate the segmental differences in expression and activation of β-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 β-adrenoceptors in the rat and human distal colon. Short-circuit current measurements (Isc) were used to assess the role of β-adrenoceptors in ion transport.


RESULTS
DA and NE caused greater suppression of baseline Isc in distal colon adjacent to the rectum than in segments further away from the anus. These responses were inhibited by selective antagonists of β₁- and β₂-adrenoceptors, but not β₃-adrenoceptor. The expression levels of β₁- and β₂-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 ΔIsc and the expression of β-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 ΔIsc as well as the expression of β-adrenoceptors were significantly enhanced in the rat colorectum but not in more proximal regions of the distal colon.


CONCLUSIONS
β₁- and β₂-adrenoceptors are predominantly expressed in the colorectal mucosa. Perturbation of endogenous catecholamine levels influences the expression and activation of β-adrenoceptors in the colorectal region.
Zhang
X H
XH
Department of Physiology, School of Basic Medical Sciences, Capital Medical University, Beijing, China.
Ji
T
T
Guo
H
H
Liu
S M
SM
Li
Y
Y
Zheng
L F
LF
Zhang
Y
Y
Zhang
X F
XF
Duan
D P
DP
D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D015153:Blotting, Western; D002395:Catecholamines / Q000494:pharmacology; D003106:Colon / Q000378:metabolism*; D018076:DNA, Complementary / Q000096:biosynthesis; D015194:Diffusion Chambers, Culture; D005455:Fluorescent Antibody Technique; D006801:Humans; D066298:In Vitro Techniques; D007413:Intestinal Mucosa / Q000378:metabolism*; D008297:Male; D012313:RNA / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D011943:Receptors, Adrenergic, beta / Q000096:biosynthesis*; D012007:Rectum / Q000378:metabolism*; D012149:Restraint, Physical; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013315:Stress, Psychological / Q000503:physiopathology; D013563:Sympathectomy, Chemical
D000318:Adrenergic beta-Agonists; D002395:Catecholamines; D018076:DNA, Complementary; D011943:Receptors, Adrenergic, beta; D012313:RNA