AJP - Gastrointestinal and Liver Physiology, Vol 264, Issue 3 522-G527, Copyright © 1993 by American Physiological Society
Thyrotropin-releasing hormone: an inhibitory regulatory peptide of feline lower esophageal sphincter
H. P. Parkman, J. C. Reynolds, C. P. Ogorek and M. S. Kreider
Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia 19104.
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)
