Abstract
We previously showed that the somatostatin receptor 5 (sst5)-preferring agonist BIM-23052 injected intracisternally (i.c.; 0.8 nmol/rat) stimulated gastric emptying of a non-nutrient meal in conscious rats. In this study, we investigated the neural pathways and specificity of BIM-23052 action. BIM-23052 (0.4, 0.8, and 1.2 nmol/rat i.c.) stimulated gastric transit; values of gastric emptying were 65.5 ± 6.5, 77.4 ± 5.3, and 77.7 ± 1.9%, respectively, compared with 43.2 ±3.2% in i.c. saline group. Intravenous injection of BIM-23052 (0.8 nmol/rat) had no effect. BIM-23052 (0.8 nmol/rat i.c.) action was prevented by subdiaphragmatic vagotomy or atropine. Medullary thyrotropin-releasing hormone (TRH) is known to play a physiological role in the vagal stimulation of gastric motor function. TRH receptor antisense oligodeoxynucleotides injected i.c. with a regimen that prevented TRH (0.3 nmol/rat i.c.)-induced enhanced gastric emptying did not influence BIM-23052 stimulatory action. Somatostatin-28 (0.2–1.2 nmol/rat i.c.), which possesses a higher affinity than somatostatin-14 for sst5, and the cyclic octapeptide des-AA1,2,4,5,12,13[d-Trp8]somatostatin (0.2–1.2 nmol/rat i.c.), an oligo-somatostatin analog that shares similar brain actions as somatostatin-28, induced a dose-related stimulation of gastric emptying. Somatostatin-14 and the preferring peptide agonists for sst1, CH-275; sst2, DC-32-87; sst3, BIM-23056 and L-796,778; and sst4, L-803,087 had no significant effect on gastric emptying when injected i.c. at 0.8 nmol/rat. These results show that BIM-23056 injected i.c. acts in the brain independently from medullary TRH to induce a vagal cholinergic stimulation of gastric emptying through the sst5 receptor subtype.
Footnotes
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Send reprint requests to: Yvette Taché, Ph.D., CURE: Digestive Diseases Research Center, Bldg. 115, Room 203, VA Greater Los Angeles Healthcare System, 11301 Wilshire Blvd., Los Angeles, CA 90073. E-mail: ytache{at}ucla.edu
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↵1 This study was supported by the National Institute of Diabetes and Digestive and Kidney Diseases Grants DK-33061 (to Y.T), DK-41301 (Center Grant, Animal Core, to Y.T.), and DK-50124 (to J.R.).
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↵2 Current address: Centro de Estudios Universitarios San Pablo, Veterinary School, Department of Physiology, 46113-Moncada, Valencia, Spain. E-mail: vmartine{at}ceu.upv.es
- Abbreviations:
- sst
- somatostatin receptor subtype
- ODT8-SST
- des-AA1,2,4,5,12,13[d-Trp8]somatostatin
- i.c.
- intracisternal
- DMN
- dorsal motor nucleus of the vagus
- TRH
- thyrotropin-releasing hormone
- CSF
- cerebrospinal fluid
- Received August 30, 1999.
- Accepted March 3, 2000.
- The American Society for Pharmacology and Experimental Therapeutics
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