Beta-adrenoceptors, but not dopamine receptors, mediate dopamine-induced ion transport in late distal colon of rats.
Dopamine, an important modulator in the gastrointestinal system, induces concentration-dependent transepithelial ion transport in the distal colon of the rat, as shown by a decrease in the short-circuit current, and acts in a segmentally dependent manner. However, the receptor(s) that mediates dopamine-induced ion transport is unknown. We have investigated the receptor mechanisms underlying dopamine-induced colonic ion transport by means of short-circuit current recording, real-time polymerase chain reaction, and Western blotting analysis, plus gene transfection and enzyme-linked immunosorbance assay. mRNA transcripts of adrenoceptors (alpha, beta) and dopaminergic receptors (D(1) and D(2)) were detected in the rat late distal colonic mucosa, with beta(2) displaying the highest expression. A similar result was found in human colorectal mucosa (equivalent of late distal colon in rat). Pretreatment with a beta(1)-adrenoceptor antagonist (CGP-20712A) and a beta(2)-adrenoceptor antagonist (ICI 118,551) inhibited the dopamine-induced short-circuit current response by 52.59% and 92.51%, respectively. However, neither dopamine D(1) receptor antagonist SCH-23390 nor dopamine D(2) receptor antagonist sulpiride blocked the effect of dopamine. Protein expression of both beta(1)- and beta(2)-adrenoceptors was found in the mucosa of rat distal colon and human sigmoid colon and rectum. Dopamine significantly increased intracellular cAMP levels in COS-7 cells transfected with beta(1)- or beta(2)-adrenoceptors. Thus, beta-adrenoceptors (mainly beta(2)-adrenoceptors), but not dopamine receptors, mediate dopamine-induced ion transport in the late distal colon of the rat. This extends our knowledge of the late distal colon (rats) or colorectum (human) and provides further experimental evidence that might aid the prevention, diagnosis, and clinical therapy of human colorectal diseases.
Zhang
Xiao-Hui
XH
Department of Physiology, School of Basic Medical Sciences, Capital Medical University, Beijing, 100069, People's Republic of China. zhangxiaohui_111@163.com
Zhang
Xie-Fu
XF
Zhang
Jiu-Qin
JQ
Tian
Yue-Min
YM
Xue
Hong
H
Yang
Ning
N
Zhu
Jin-Xia
JX
D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D003106:Colon / Q000166:cytology / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism*; D017136:Ion Transport / Q000502:physiology; D007477:Ions / Q000378:metabolism; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D011943:Receptors, Adrenergic, beta / Q000235:genetics / Q000378:metabolism*; D011954:Receptors, Dopamine / Q000378:metabolism*
D007477:Ions; D011943:Receptors, Adrenergic, beta; D011954:Receptors, Dopamine; D004298:Dopamine