Pathways mediating pentagastrin-induced mucosal blood flow response in rat stomachs.
The mechanisms of pentagastrin-induced gastric mucosal blood flow (GMBF) response were investigated in anesthetized rats. A rat stomach was mounted on an ex vivo chamber, perfused with saline, and GMBF was measured by a laser Doppler flowmetry simultaneously with acid secretion. Pentagastrin infused intravenously produced a dose-dependent increase of GMBF as well as acid secretion, and its effect reached a maximum at 120 microgram/kg/hr (maximal dose). Pretreatment with omeprazole (60 mg/kg, intraperitoneally) completely inhibited the acid secretory response and the enhancement of GMBF induced by both submaximal (60 micrograms/kg/hr) and maximal doses of pentagastrin. In contrast, the luminal perfusion with glycine (200 mM) to remove luminal H+ almost totally attenuated the increase of GMBF caused by the submaximal dose of pentagastrin, without any effect on acid secretion, but partially suppressed such GMBF responses caused by the maximal dose. Subcutaneous pretreatment with indomethacin, a cyclooxygenase inhibitor, significantly mitigated GMBF response caused by both submaximal and maximal doses of pentagastrin, whereas 8-phenyltheophylline (8-PT), an adenosine antagonist, showed a significant inhibition of GMBF response caused by only the maximal dose. However, the combined administration of 8-PT with glycine perfusion further attenuated GMBF response caused by the maximal dose of pentagastrin, and the additional treatment with indomethacin completely blocked this this GMBF response. We conclude that pentagastrin-induced GMBF responses are mediated by at least two different pathways; one is related to luminal H+ and the other to the parietal cell activity, depending on the dose of pentagastrin. In addition, the latter pathway may be mediated by adenosine, while endogenous prostaglandins may be involved in both pathways.
Kato
S
S
Department of Pharmacology and Experimental Therapeutics, Kyoto Pharmaceutical University, Japan.
Okabe
S
S
Takeuchi
K
K
D000818:Animals; D000897:Anti-Ulcer Agents / Q000008:administration & dosage / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005744:Gastric Acid / Q000378:metabolism; D005753:Gastric Mucosa / Q000098:blood supply* / Q000187:drug effects* / Q000378:metabolism; D005998:Glycine / Q000008:administration & dosage / Q000494:pharmacology; D007213:Indomethacin / Q000008:administration & dosage / Q000494:pharmacology; D008297:Male; D009853:Omeprazole / Q000008:administration & dosage / Q000494:pharmacology; D010418:Pentagastrin / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow / Q000187:drug effects; D013806:Theophylline / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology
D000897:Anti-Ulcer Agents; D013806:Theophylline; C028322:8-phenyltheophylline; D010418:Pentagastrin; D009853:Omeprazole; D005998:Glycine; D007213:Indomethacin