Endothelin receptors in human and guinea-pig gallbladder muscle.
We measured contraction of muscle strips caused by endothelin (ET) isopeptides and binding of (125)I-ET-1 to muscle cell membranes prepared from human and guinea-pig gallbladders. Visualization of (125)I-ET-1 binding sites in tissue was performed by autoradiography. Results in human were similar to those in guinea-pig. ET-1 caused tetrodotoxin and atropine-insensitive contraction. The relative potencies for ET isopeptides to cause contraction were ET-1=ET-2>ET-3. ET-1 caused contraction was only slightly inhibited by BQ-123 (potent ET(A) receptor antagonist) and not by BQ-788 (potent ET(B) receptor antagonist). It was inhibited by the combination of both. Autoradiography localized (125)I-ET-1 binding to the smooth muscle layer. Binding of (125)I-ET-1 to muscle cell membranes was saturable and specific. Analysis of dose-inhibition curves demonstrated the presence of two classes of receptors. One class (ET(A) receptor) had a high affinity for ET-1 and ET-2 but a low affinity for ET-3, and the other (ET(B) receptor) a high affinity for ET-1, ET-2 and ET-3. These results demonstrate that similar to guinea-pig, human gallbladder possesses both ET(A) and ET(B) receptors cooperating to mediate muscle contraction.
Department of Internal Medicine, Tzu Chi General Hospital and Tzu Chi University, 707 Section 3, Chung-Yang Road, 970, Taiwan, Hualien, China. shihche@mail.tcu.edu.tw
S C
SC
Huang
M C
MC
Lee
C K
CK
Wei
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SM
Huang
D000328:Adult; D000368:Aged; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001345:Autoradiography; D001667:Binding, Competitive; D002462:Cell Membrane / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D065128:Endothelin Receptor Antagonists; D016232:Endothelins / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000494:pharmacology; D005260:Female; D005704:Gallbladder / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D006168:Guinea Pigs; D006801:Humans; D008297:Male; D008875:Middle Aged; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009842:Oligopeptides / Q000494:pharmacology; D010456:Peptides, Cyclic / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D020033:Protein Isoforms / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000494:pharmacology; D017466:Receptors, Endothelin / Q000819:agonists / Q000378:metabolism*; D013379:Substrate Specificity; D013779:Tetrodotoxin / Q000494:pharmacology
D065128:Endothelin Receptor Antagonists; D016232:Endothelins; D009842:Oligopeptides; D010456:Peptides, Cyclic; D010880:Piperidines; D020033:Protein Isoforms; D017466:Receptors, Endothelin; D013779:Tetrodotoxin; C086539:BQ 788; D001285:Atropine; C072247:cyclo(Trp-Asp-Pro-Val-Leu)