Role of adenosine in the gastric blood flow response to pentagastrin in the rat.
We tested the hypothesis that the increase in gastric mucosal blood flow during pentagastrin-stimulated acid secretion in the rat is mediated partly by endogenously generated adenosine. In in vivo microscopic studies, topical 10(-5) to 10(-3) M adenosine dose-dependently dilated the submucosal arterioles, the vessels that control mucosal blood flow. The adenosine receptor antagonist 8-phenyltheophylline, significantly reduced adenosine's vasodilatory response. An adenosine analog with a high A2 receptor affinity was 100 times more potent as a vasodilator than one with a high A1 receptor affinity but lower A2 receptor affinity. We then examined the effect of i.v. 8-phenyltheophylline, 10 mg/kg, on the pentagastrin-stimulated increase in gastric blood flow and gastric acid secretion. Mucosal blood flow was estimated by the hydrogen clearance technique. Pentagastrin increased mucosal blood flow from 26.6 +/- 2.6 to 42.7 +/- 4.9 ml/min/100 g and this was reduced to 31.9 +/- 3.1 ml/min/100 g upon the addition of 8-phenyltheophylline. Gastric acid secretion upon the addition of 8-phenyltheophylline. Gastric acid secretion was stimulated by pentagastrin and stimulated further by the addition of 8-phenyltheophylline from 2.06 +/- 0.34 mEq of H+ per min to 2.84 +/- 0.49 mEq/min. 8-Phenyltheophylline had no effect on basal mucosal blood flow or gastric acid secretion. In contrast, the nonmethylxanthine phosphodiesterase inhibitor RO 20-1724 stimulated acid secretion and increased gastric mucosal blood flow during pentagastrin administration. The data suggest that gastric submucosal arterioles contain adenosine receptors of the A2 subtype that vasodilate when activated.(ABSTRACT TRUNCATED AT 250 WORDS)
Gerber
J G
JG
Medical Service, Wadsworth Hospital, Los Angeles, California.
Guth
P H
PH
D000241:Adenosine / Q000502:physiology*; D000818:Animals; D005744:Gastric Acid / Q000378:metabolism; D005753:Gastric Mucosa / Q000098:blood supply / Q000187:drug effects*; D008297:Male; D010418:Pentagastrin / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012039:Regional Blood Flow / Q000187:drug effects; D013806:Theophylline / Q000031:analogs & derivatives / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects
D013806:Theophylline; C028322:8-phenyltheophylline; D010418:Pentagastrin; D000241:Adenosine