Central vagal activation by TRH induces gastric hyperemia: role of CGRP in capsaicin-sensitive afferents in rats.
The role of calcitonin gene-related peptide (CGRP) in the vagal cholinergic-mediated increase in gastric mucosal blood flow (GMBF) induced by the stable thyrotropin-releasing hormone (TRH) analogue RX-77368 injected intracisternally (ic, 30 ng) was investigated in urethan-anesthetized rats using the hydrogen gas clearance technique. alpha-CGRP (14 micrograms.kg-1.h-1) or bethanechol (150 micrograms.kg-1.h-1) infused close intra-arterially to the stomach or RX-77368 injected intracisternally increased GMBF by 76, 102, and 131%, respectively, 30 min after administration. The CGRP antagonist, human CGRP-(8-37) [hCGRP-(8-37)], injected intravenously (15 micrograms/kg bolus and 3 micrograms.kg-1.h-1) inhibited by 100, 97, and 73% the gastric hyperemic response to alpha-CGRP, TRH analogue, and bethanechol, respectively, whereas the substance P antagonist CP-96,345 (3 mg/kg iv) had no effect. In capsaicin-pretreated rats, hCGRP-(8-37) no longer blocked the increase in GMBF induced by intracisternal RX-77368. These results suggest that the gastric hyperemic response to central vagal activation induced by intracisternal TRH analogue at 30 ng is mediated by local effector function of capsaicin-sensitive afferent fibers releasing CGRP.
Kiràly
A
A
Center for Ulcer Research and Education/University of California Los Angeles Gastroenteric Biology Center.
Sütö
G
G
Livingston
E H
EH
Guth
P H
PH
St Pierre
S
S
Taché
Y
Y
D000818:Animals; D018723:Bethanechol / Q000494:pharmacology; D001713:Biphenyl Compounds / Q000494:pharmacology; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology / Q000502:physiology*; D000077221:Calcitonin Gene-Related Peptide Receptor Antagonists; D002211:Capsaicin / Q000494:pharmacology*; D005753:Gastric Mucosa / Q000098:blood supply*; D006940:Hyperemia / Q000209:etiology*; D008297:Male; D010446:Peptide Fragments / Q000494:pharmacology; D011761:Pyrrolidonecarboxylic Acid / Q000031:analogs & derivatives; D051381:Rats; D017207:Rats, Sprague-Dawley; D013973:Thyrotropin-Releasing Hormone / Q000031:analogs & derivatives / Q000494:pharmacology*; D014630:Vagus Nerve / Q000502:physiology*
D001713:Biphenyl Compounds; D000077221:Calcitonin Gene-Related Peptide Receptor Antagonists; D010446:Peptide Fragments; D018723:Bethanechol; C058636:calcitonin gene-related peptide (8-37); D013973:Thyrotropin-Releasing Hormone; C027979:L-pyroglutamyl-L-histidyl-3,3-dimethylprolinamide; D015740:Calcitonin Gene-Related Peptide; D002211:Capsaicin; D011761:Pyrrolidonecarboxylic Acid; C066892:CP 96345