Vol. 293, Issue 3, 1099-1105, June 2000

Intracisternal Injection of Somatostatin Receptor 5-Preferring Agonists Induces a Vagal Cholinergic Stimulation of Gastric Emptying in Rats¹

Vicente Martínez² , Jean Rivier, David Coy and Yvette Taché

CURE: Digestive Diseases Research Center, VA Greater Los Angeles Healthcare System, Department of Medicine, Digestive Diseases Division and Brain Research Institute, UCLA School of Medicine, Los Angeles, California (V.M., Y.T.); Clayton Foundation Laboratories for Peptide Biology, Salk Institute for Biological Studies, La Jolla, California (J.R.); and Peptide Research Laboratories, Department of Medicine, Tulane University Medical Center, New Orleans, Louisiana (D.C.)

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-AA^{1,2,4,5,12,13}[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.