INTERACTIONS BETWEEN HISTAMINERGIC AND CHOLINERGIC PATHWAYS OF GASTRIC-MOTILITY REGULATION

Smooth muscle preparations, isolated in a circular direction from guin ea pig gastric fundus, were used to study the effects of H-1 and H-2 a ntagonists on acetylcholine (AGH)- and histamine (HA)-induced contract ions as yell as the effects of HA antagonists on spontaneous contracti le activity. HA (1 x 10(-9) M to 1 x 10(-5) M) concentration-dependent ly enhanced the tone of the strips with ED(50) = 3.5 x 10(-7) M. Appli ed 5 min before HA, the H-1 antagonists (mepyramine, diphenhydramine, dimethpyrindene) and the H-2 blockers (ranitidine, cimetidine, roxatid ine) reduced HA-induced contractions. HA in concentrations of 1 x 10(- 8) M to 1 x 10(-7) M potentiated and in higher concentrations (1 x 10( -6) M to 1 x 10(-5) M) inhibited, smooth muscle contractions evoked by low frequency electrical field stimulation (EFS). The H-1 blockers (1 x 10(-6) M to 1 x 10(-4) M) concentration-dependently enhanced smooth muscle tone, the maximum contractions being about 50% smaller than th e contractile responses to I x 10(-5) MACH and 5 x 10(-5) M HA. Tetrod otoxin, atropine and indomethacin shifted to the light the concentrati on-response curve for mepyramine, reducing its maximum by 25, 58 and 6 2%, respectively. The H-2 blocker ranitidine also suppressed (by 42%) mepyramine-evoked increase in the fundic strips tone. The H-1 antagoni sts reduced AGH-induced contractions of the smooth muscle strips and d id not affect the contractions in response to EFS. The H-2 blockers ha d no effect on tone and ACH-evoked contractions of the smooth muscle s trips but concentration-dependently enhanced both the contractions and [H-3]-ACH release in response to EFS. The results demonstrate the pre sence of both H-1 and H-2 postsynaptic receptors which are involved in the direct myogenic action of HA on guinea pig gastric fundus smooth muscles. It also appears that HA might concentration-dependently modul ate the cholinergic neurotransmission ill gastric fundus. It could be suggested that H-1 blockers have a direct myogenic effect on guinea pi g gastric fundus smooth muscle and might also interact postsynapticall y with muscarinic receptors in this tissue.