Intracisternal injection of somatostatin receptor 5-preferring agonists induces a vagal cholinergic stimulation of gastric emptying in rats.
We previously showed that the somatostatin receptor 5 (sst(5))-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 sst(5), and the cyclic octapeptide des-AA(1,2,4,5,12,13)[D-Trp(8)]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 sst(1), CH-275; sst(2), DC-32-87; sst(3), BIM-23056 and L-796,778; and sst(4), 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 sst(5) receptor subtype.
Martínez
V
V
CURE: Digestive Diseases Research Center, VA Greater Los Angeles Healthcare System, Los Angeles, CA 90073, USA. vmartine@ceu.upv.es
Rivier
J
J
Coy
D
D
Taché
Y
Y
D000818:Animals; D001285:Atropine / Q000494:pharmacology; D002946:Cisterna Magna / Q000187:drug effects*; D005746:Gastric Emptying / Q000187:drug effects*; D008297:Male; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D009842:Oligopeptides / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017481:Receptors, Somatostatin / Q000037:antagonists & inhibitors*; D018025:Receptors, Thyrotropin-Releasing Hormone / Q000502:physiology; D013004:Somatostatin / Q000031:analogs & derivatives* / Q000494:pharmacology; D014630:Vagus Nerve / Q000502:physiology*
C114314:BIM 23052; C091737:BIM 23056; D016376:Oligonucleotides, Antisense; D009842:Oligopeptides; D017481:Receptors, Somatostatin; D018025:Receptors, Thyrotropin-Releasing Hormone; D013004:Somatostatin; D001285:Atropine; C094573:somatostatin receptor 5