SMS 201-995-induced stimulation of gastric acid secretion via the dorsal vagal complex and inhibition via the hypothalamus in anaesthetized rats

Yoneda, M.; Taché, Y.

British Journal of Pharmacology 116(4): 2303-2309

1995


ISSN/ISBN: 0007-1188
PMID: 8564264
DOI: 10.1111/j.1476-5381.1995.tb15069.x
Accession: 009375164

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Abstract
1. SMS 201-995, a somatostatin analogue which interacts with highest affinities at somatostatin receptor subtypes 5 > 2 > or = 3, was microinjected into selective brain sites and its influence on pentagastrin (10 micrograms kg-1 h-1, i.v.)-stimulated gastric acid secretion was investigated in rats anaesthetized with urethane. Gastric acid secretion was measured by flushing the stomach with saline through a gastric cannula every 10 min. 2. SMS 201-995 microinjected into the dorsal vagal complex (DVC, 7, 15, 30 and 60 ng) dose-dependently increased pentagastrin-stimulated gastric acid secretion. The peak acid response was reached within 20 min and returned to basal level 50 min post-injection. SMA 201-995 (30 ng) microinjected into the surrounding area or the central amygdala did not modify pentagastrin-stimulated acid secretion. 3. SMS 201-995 injected into the lateral ventricle (i.c.v., 100, 200, or 300 ng), paraventricular nucleus (PVN) or lateral hypothalamus (LH) (7.5, 15, or 30 ng) dose-dependently inhibited pentagastrin-stimulated gastric acid secretion. SMS 201-995 (30 ng) microinjected into the area surrounding the PVN or LH did not modify the acid secretion response to pentagastrin. 4. Vagotomy prevented the effects of SMS 201-995 (30 ng) microinjected into the DVC and LH. 5. Spinal cord transection abolished the inhibitory action of SMS 201-995 (30 ng) microinjected into the PVN but not the LH. 6. These results demonstrate that SMS 201-995 acts in the DVC to enhance and in the LH and PVN to inhibit pentagastrin-stimulated gastric acid secretion. The action is mediated through vagal (DVC, LH)or spinal (PVN) pathways. The site specific pattern of acid responses to SMS 201-995 may be linked to the distribution of receptor subtypes at these sites that convey the different biological actions of somatostatin.

SMS 201-995-induced stimulation of gastric acid secretion via the dorsal vagal complex and inhibition via the hypothalamus in anaesthetized rats