A comparison of the effects of sympathomimetic agents on gastric acid secretion by the rat stomach in vivo and in vitro.

1. The action of isoprenaline on gastric acid secretion in rats with Heidenhain pouches has been compared with its action in a rat isolated stomach preparation. 2. Isoprenaline (40 micrograms kg-1 h-1) inhibited the acid secretion in response to pentagastrin (20 micrograms kg-1 h-1) in conscious rate with Heidenhain pouches. 3. This inhibition could be abolished by propranolol (2 mg kg-1) and butoxamine (8 mg kg-1) and partially reversed by practolol (8 mg kg-1). 4. Propranolol (2 mg kg-1) significantly increased the response to pentagastrin (20 micrograms kt-1 h-1) but butoxamine and practolol (both at 8 mg kg-1) and the inactive isomer (+)-propranolol (2 mg kg-1) were without any effect on the pentagastrin response in the rats with pouches. 5. In the rat isolated stomach preparation isoprenaline stimulated acid secretion over the range 10(-7) M-10(-3) M whereas phenylephrine and methoxamine were without effect. 6. Propranolol (2 X 10(-5) M) inhibited this stimulatory effect of isoprenaline in vitro but (+)-propranolol (2 X 10(-5) M), practolol and butoxamine (both at 10(-4) M) had no effect on the response. 7. Propranolol (2 X 10(-5) M) did not have any effect on the response of the isolated stomach to pentagastrin (5 X 10(-7) M) or bethanechol (1.7 X 10(-5) M). 8. Phenylephrine (2 X 10(-5) M) did not affect the in vitro responses to pentagastrin (2.17 X 10(-7) M), bethanechol (1.7 X 10(-5) M) or histamine (5.4 X 10(-5) M). 9. It is concluded that isoprenaline has a direct stimulatory effect and an indirect inhibitory effect on gastric acid secretion in the rat. Both effects involve stimulation of beta-adrenoceptors. The relative predominance of one or other of these two opposing effects may help to explain the contradictory results in the literature regarding the actions of beta-adrenoceptor agonists on gastric acid secretion.