5-HT in DVC: disparate effects on TRH analogue-stimulated gastric acid secretion, motility, and cytoprotection.
Convergent evidence suggests that thyrotropin-releasing hormone (TRH) is a principal regulator of several vagally mediated gastric responses. Serotonin (5-HT) interacts with TRH in the dorsal vagal complex (DVC) to augment gastric acid secretory responses. This study investigated the ability of 5-HT to alter other gastric responses mediated by TRH administration into the DVC. Co-injection of 5-HT (7.9 pmol) and the TRH analogue RX-77368 (0.66 pmol) produced a 117% enhancement in 1-h gastric acid output compared with rats treated with RX-77368 (0.66 pmol) alone into the DVC. In contrast, coadministration of RX-77368 (4 pmol) with various doses of 5-HT (0.0048-480 pmol) was ineffective in significantly altering stimulation of gastric antral motility produced by RX-77368 (4 pmol) alone. The effect of a lower dose of DVC RX-77368 (0.66 pmol) on gastric motility was also not changed by 5-HT coadministration. Moreover, the cytoprotective effect of DVC RX-77368 (1.5 pmol) on oral ethanol-induced gastric mucosal lesions was reversed by 5-HT coadministration (54 or 18 pmol). The results suggest that activation of 5-HT receptors in the DVC can augment, not affect, and attenuate DVC TRH analogue-stimulated gastric acid secretion, antral motility, and cytoprotection, respectively.
Chi
J
J
Department of Physiology, Ohio State University, Columbus 43210, USA.
Kemerer
J
J
Stephens
R L
RL
D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000502:physiology*; D005744:Gastric Acid / Q000378:metabolism*; D005769:Gastrointestinal Motility / Q000187:drug effects; D008297:Male; D011761:Pyrrolidonecarboxylic Acid / Q000031:analogs & derivatives; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000494:pharmacology*; D017552:Solitary Nucleus / Q000187:drug effects* / Q000502:physiology*; D013270:Stomach / Q000166:cytology / Q000187:drug effects; D013973:Thyrotropin-Releasing Hormone / Q000031:analogs & derivatives / Q000494:pharmacology; D014630:Vagus Nerve / Q000502:physiology*
D012701:Serotonin; D013973:Thyrotropin-Releasing Hormone; C027979:L-pyroglutamyl-L-histidyl-3,3-dimethylprolinamide; D011761:Pyrrolidonecarboxylic Acid