SMS 201-995-induced stimulation of gastric acid secretion via the dorsal vagal complex and inhibition via the hypothalamus in anaesthetized rats.
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.
Yoneda
M
M
CURE/Gastroenteric Biology Center, West Los Angeles VA Medical Center, CA 90073, USA.
Taché
Y
Y
D000595:Amino Acid Sequence; D000758:Anesthesia; D000818:Animals; D005744:Gastric Acid / Q000378:metabolism*; D005765:Gastrointestinal Agents / Q000008:administration & dosage / Q000494:pharmacology*; D007031:Hypothalamus / Q000187:drug effects / Q000502:physiology*; D007276:Injections, Intraventricular; D008032:Limbic System / Q000502:physiology; D008297:Male; D008526:Medulla Oblongata / Q000033:anatomy & histology / Q000502:physiology; D008845:Microinjections; D008969:Molecular Sequence Data; D015282:Octreotide / Q000008:administration & dosage / Q000494:pharmacology*; D010418:Pentagastrin / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000502:physiology; D014628:Vagotomy; D014630:Vagus Nerve / Q000187:drug effects / Q000502:physiology*
D005765:Gastrointestinal Agents; D010418:Pentagastrin; D015282:Octreotide