Medullary sites for TRH analogue stimulation of gastric contractility in the rat

Abstract

Medullary sites at which the stable thyrotropin-releasing hormone (TRH) analogue, RX 77368 (p-Glu-His-[3,3'-dimethyl]-Pro-NH2), stimulates gastric contractility were investigated in rats under urethan anesthesia. The peptide analogue was microinjected in 50-100 nl of volume unilaterally into various brain stem nuclei using glass micropipettes (50 microns). Gastric contractility was recorded continuously with acutely implanted strain-gauge force transducers and traces analyzed by computer. RX 77368 (2.6-77 pmol) microinjected into the dorsal vagal complex (DVC) dose dependently stimulated gastric contractility. Peptide action (77 pmol) had a rapid onset with a peak response at 15 min, continued for 45 min after the microinjection, and was blocked by vagotomy. TRH microinjected into the DVC had a shorter duration of action. RX 77368 (0.7-77 pmol) microinjected into the nucleus ambiguus also dose dependently stimulated gastric contractions. In contrast, microinjection of RX 77368 (77 pmol) into the hypoglossal nucleus had no effect. These findings demonstrate that the DVC and nucleus ambiguus are sites of action for TRH-induced stimulation of gastric contractility in the rat. The effect is dose dependent, long lasting, site specific, and vagally mediated. These results are consistent with a possible physiological role for medullary TRH in the vagal regulation of gastric contractility.

From simplicity to complexity (1950–1990): the case of peptic ulceration—II. Animal studies.

“…Injection of various doses up to 100 ng of RX 77368 into the DVM, NA, and n. raphe pallidus and obscurus produces a dosedependent and rapid increase (peaking after 15 min) in slow gastric contractions which last 1 hr (115,116). Injection of various doses up to 100 ng of RX 77368 into the DVM, NA, and n. raphe pallidus and obscurus produces a dosedependent and rapid increase (peaking after 15 min) in slow gastric contractions which last 1 hr (115,116).…”

Central and peripheral regulation of gastric acid secretion by peptide YY

“…Chemical stimulation of the DVC, such as injecting exogenous TRH into the DVC [24,40] or increasing endogenous TRH release in the DVC via the stimulation of the raphe nuclei [23,93], induces vagally mediated elevation of gastric secretory and motor functions. However, when the DVC neurons are stimulated with subthreshold doses of these stimuli that do not change acid secretion or motility, gastric protection against ulcerations was observed.…”