Effect of Adenosine and Histamine Receptor Stimulation on Canine Histamine Release to Pentagastrin

Abstract

The effects of adenosine and histamine 2 and histamine 3 receptor agonists on the regulation of gastric histamine release were examined in anesthetized mixed-breed dogs. All compounds were infused directly into the gastrosplenic artery to avoid perturbations in systemic hemodynamics, and the gastric histamine release was stimulated with pentagastrin. The histamine concentration in plasma samples was measured utilizing gas chromatography-negative-ion chemical ionization mass spectroscopy. Pentagastrin consistently stimulated gastric histamine release with the peak stimulation occurring at 5 min, while neither 30 nor 100 μM of adenosine altered the effect of pentagastrin on histamine release. In addition, theophylline at 20 μg/ml exhibited no effect on stimulated histamine release. The histamine 2 receptor agonist dimaprit, at 1 and 3 μM, attenuated pentagastrin-stimulated histamine release at the 5-min time period, but the difference was not sustained at later time points (histamine release from 1.4 ± 0.6 to 92 ± 18 ng/min at 5 min with pentagastrin alone; from 1.2 ± 0.5 to 32 ± 11 ng/min with pentagastrin plus 1 μM dimaprit, and from 2.0 ± 1.1 to 32 ± 9 ng/min with pentagastrin plus 3 μM dimaprit), while the H₂ receptor antagonist cimetidine exhibited no effect on pentagastrin-stimulated histamine release. The histamine 3 receptor agonist (R)-α-methyl-histamine attenuated the pentagastrin-stimulated histamine release at the 5-and 10-min time periods only at 1 μM without showing any effect at the higher (3 μM) concentration. Thioperamide, a H₃ receptor antagonist, did not modify pentagastrin-stimulated histamine release. These data demonstrate that adenosine has no modulatory role on gastric histamine release, but histamine via H₂ and H₃ histamine receptors could modulate its own release but only to a modest degree as compared with the potent effect of the paracrine hormone somatostatin.