Central nervous system action of calcitonin gene-related peptide to inhibit gastric emptying in the conscious rat.
The central nervous system action of rat alpha-calcitonin gene-related peptide (alpha-CGRP) on gastric emptying of a liquid, noncaloric, methylcellulose solution was assessed in 24-hr fasted, conscious rats using phenol red method as a marker. Intracisternal injection of alpha-CGRP (0.75-250 pmol) dose-dependently inhibited gastric emptying by 27-94% as measured 20 min after oral administration of the solution. The ED50 was 6.2 pmol. alpha-CGRP injected intravenously at 250 pmol delayed gastric emptying by 71% whereas a lower dose (75 pmol) was inactive. Intracisternal alpha-CGRP-induced inhibition of gastric emptying was completely abolished by bilateral adrenalectomy and partially suppressed by subdiaphragmatic vagotomy or coeliac/superior mesenteric ganglionectomy. Adrenalectomy or vagotomy in saline-treated animals did not significantly modify the rate of gastric emptying whereas coeliac/superior mesenteric ganglionectomy caused a significant 29% inhibition as compared to the nonoperated group. These results demonstrate that alpha-CGRP is a potent centrally acting inhibitor of gastric emptying of a nonnutrient liquid. The inhibitory effect of intracisternal injection of CGRP appears to be mediated by the adrenal gland and in part by the sympathetic and parasympathetic nervous system.
Raybould
H E
HE
Center for Ulcer Research and Education, Wadsworth VA Medical Center, Los Angeles, CA 90073.
Kolve
E
E
Taché
Y
Y
D000315:Adrenalectomy; D000818:Animals; D002116:Calcitonin / Q000494:pharmacology*; D015740:Calcitonin Gene-Related Peptide; D002946:Cisterna Magna / Q000187:drug effects / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D005746:Gastric Emptying / Q000187:drug effects*; D007267:Injections; D007275:Injections, Intravenous; D008297:Male; D009479:Neuropeptides / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values; D014628:Vagotomy
D009479:Neuropeptides; D002116:Calcitonin; D015740:Calcitonin Gene-Related Peptide