Different effects of H-1 and H-2 blockers on the tone and the contractile activity of guinea pig stomach fundus

The action of H-1 and H-2 blockers on the spontaneous and evoked contractile activity of gastric fundus smooth muscles as well as the effects of H-2 antagonists on the release of acetylcholine (ACh) from gastric myenteric neurons were studied. The experiments were performed on smooth muscle strips (25x3 mm) cut out in circular direction from guinea pig fundus region. In concentrations of 1x10(-7) M to 1x10(-4) M, the H-1 blockers diphenhydramine (DPH), mepyramine (MEP) and dimethpyrindene (DMPD), but not the H-2 blockers ranitidine (RAN), cimetidine (CIM) and roxatidine (ROX), increased in a concentration-dependent manner the smooth muscle tone, the maximum contractions being about 50% of the the contractile effects of 1x10(-5) MACH and 5x10(-5) M histamine (HA). The concentration-dependent contractions of the stomach fundus strips in response to electrical field stimulation (EFS) were enhanced by RAN, CIM and ROX (but nor by MEP and DPH), all in concentrations of 1x10(-7) M to 1x10(-4) M EFS increased the resting [H-3]-ACh release by 67.8%, the S-2/S-1 ratio being 0.85 +/- 0.04. ROX in a concentration of 1x10(-5) M significantly increased (by 16.1%) the EFS-induced release with a S-2/S-1 ratio of 1.22 +/- 0.04. The ROX effect on the [H-3]-ACh release was reduced or even abolished by 1x10(-6) M tetrodotoxin (TTX) and 1x10(-6) M scopolamine or in Ca2+-free medium, while 1x10(-6) M hexamethonium did not change it. It might be concluded that H-2 blockers have no direct myogenic effect and do not interfere with muscarinic receptors in guinea pig stomach fundus. The H-2 antagonists enhance the EFS-evoked contractions of the gastric smooth muscle most probably by increasing the release of ACH.