Adenosine receptors on canine parietal cells modulate gastric acid secretion to histamine
Gerber, J.G.; Nies, A.S.; Payne, N.A.
Journal of Pharmacology and Experimental Therapeutics 233(3): 623-627
1985
ISSN/ISBN: 0022-3565 PMID: 2409269 Document Number: 259277
Administration of theophylline has been shown to enhance gastric acid secretion in humans. Because theophylline has been reported to be a poor inhibitor of phosphodiesterase but a better adenosine receptor antagonist, the hypothesis that there are inhibitory "R site" adenosine receptors on parietal cells were tested. Isolated dispersed canine parietal cells were used to measure acid secretion by the [14C]aminopyrine accumulation technique. The effect of increasing concentrations of 2-chloroadenosine (10-7, 10-6, 10-5 M) and L-N6-phenylisopropyladenosine (L-PIA) (10-7, 10-6 and 10-5 M), stable analogs of adenosine with specificity of the R sites were tested on aminopyrine uptake produced by submaximal stimulating concentrations of histamine (1 .mu.M) plus isobutyl methylxanthine (3 .mu.M) or carbachol (1 .mu.M). Histamine-stimulated parietal cell aminopyrine uptake was 4.3- .+-. 0.4-fold above basal; 2-chloroadenosine inhibited this response in a dose-dependent fashion with a 57 .+-. 6% inhibition at 10-5 M. L-PIA also in hibited histamine-stimulated aminopyrine uptake with a 67 .+-. 11% inhibition at 10-5 M. Carbachol-stimulated aminopyrine uptake was 5.8- .+-. 1.6-fold above basal, but 2-chloroadenosine had no significant effect on this response. Theophylline, 300 .mu.M, and 8-phenyltheophylline, 10 .mu.M, reduced the inhibitory effect of 2-chloroadenosine. 8-Phenyltheophylline iwas inactive in inhibiting the parietal cell phosphodiesterase was 1 mM. Because prostaglandins inhibit parietal cell uptake of aminopyrine in a pattern similar to 2-chloroadenosine, the possibility that prostaglandins are involved in the 2-chloroadenosine response was tested. Indomethacin at 30 .mu.M had no effect on the ability of 2-chloroadenosine to inhibit the response to histamine. In addition, L-PIA had no effect on dibutyryl cAMP-stimulated aminopyrine uptake. At a concentration of 10-7 M, L-PIA inhibited the histamine-stimulated cAMP accumulation but, at higher concentrations, the effect was lost. There apparently are inhibitory adenosine receptors of the R type on parietal cells that modulate the acid secretory response to histamine but not to cholinergic stimulation and that this effect is independent of prostaglandins. The most likely mechanism by which the adenosine analogs inhibit acid secretion is by inhibition of histamine-stimulated cAMP.