Adrenergic stimulation of isolated rat gastric mucosal cells. Effect on adenylate cyclase and 14C-aminopyrine uptake.

Adrenergic stimulation of the adenylate cyclase (AC)-cAMP-system and 14C-aminopyrine accumulation, an indirect measure of parietal cell H+-production, was studied in a different preparations of gastric mucosal cells. The beta 2-adrenoceptor agonist hexoprenaline activated AC of crude homogenates from the gastric corpus of mouse, rat, guinea-pig, hog, dog and man. In isolated rat gastric cells (20% parietal cells), treated by low power sonication, 10(-8) to 10(-3) mol/l adrenaline and hexoprenaline activated AC equally potently and efficaciously by maximally 170%. Isoprenaline proved to be less effective activating up to 80%. 5.10(-5) mol/l GMP-PNP augmented basal activity 8.5 times and reduced the maximal efficacy. Adrenaline and hexoprenaline activated AC by maximally 120%, isoprenaline by 40%. The potency of adrenaline was 4 times lower, that of hexoprenaline 2 and that of isoprenaline 4 times higher in the presence of GMP-PNP. Adrenergic stimulation was inhibited by the beta-adrenoceptor antagonist propranolol, the effect of alpha-adrenoceptor-blockade by phenoxybenzamine was less pronounced. In fractions with 7-80% of parietal cells, prepared by isopycnic centrifugation with Percoll, adrenaline and hexoprenaline activated AC or hexoprenaline enhanced the cellular levels of cAMP in parietal cell poor and rich fractions. The degree of activation in response to histamine correlated with the number of parietal cells. 14C-Aminopyrine uptake was increasingly stimulated through 10(-8) to 10(-5) mol/l hexoprenaline, maximally by doubling the basal accumulation. 10(-4) mol/l histamine was 8 times more effective. 3.10(-7) mol/l propranolol inhibited the effect of 10(-5) mol/l hexoprenaline by 80%. The data suggest the localization of beta-adrenoceptors (likely beta 2-adrenoceptors) on parietal and other nonidentified gastric cells. At the parietal cell, adrenaline and hexoprenaline initiate activation of AC and hexoprenaline leads to H+-production. The responses are small compared to the effect of histamine. Thus, beta-adrenoceptor agonists exert intrinsic activity in relation to H+-production. Their influence on stimulated secretion of isolated cells remains to be elucidated.