The functional role of thyrotropin-releasing hormone (TRH) at the lower esophageal sphincter (LES) was examined in the cat. The specific aims of this study were to determine: 1) the relative distribution of TRH throughout the feline gastrointestinal tract and 2) the effect of TRH on LES basal pressures and its response to exogenously induced contractions. TRH concentrations were determined by radioimmunoassay in tissue extracts from 12 sites. The mean concentration of TRH at the manometrically determined LES was 240 +/- 85 pg/g wet wt tissue, and the maximal concentration was just distal to the LES (659 +/- 189 pg/g wet wt). TRH concentration was higher in the mucosa than the underlying muscle layer of the fundus, antrum, duodenum, and ileum. In physiological studies, TRH given selectively via the left gastric artery had no effect on basal LES or esophageal pressures. TRH (2.8 x 10(-8) mol/kg) decreased the LES response to the D50 of substance P by 47.2% (34.8 +/- 3.1 to 18.4 +/- 2.9 mmHg, P < 0.01). In the presence of tetrodotoxin, TRH gave a similar inhibition of substance P-induced contractions (53.5%). TRH also decreased bombesin-induced contractions by 47.5% (29.6 +/- 6.0 to 15.8 +/- 3.9 mmHg, P < 0.025). TRH, however, had no effect on bethanechol-induced contractions. We conclude that 1) TRH is present throughout the gastrointestinal tract, with highest concentrations in the region distal to the LES; 2) TRH has no effect on basal LES tone; and 3) TRH inhibits the LES response to endogenously released and exogenous substance P but not the LES response to bethanechol.(ABSTRACT TRUNCATED AT 250 WORDS)
