Interactions between histaminergic and cholinergic pathways of gastric motility regulation
Milenov, K.; Todorov, S.; Vassileva, M.; Zamfirova, R.; Shahbazian, A.
Methods and Findings in Experimental and Clinical Pharmacology 18(1): 33-39
1996
ISSN/ISBN: 0379-0355 PMID: 8721254 Document Number: 1046
Smooth muscle preparations, isolated in a circular direction from guinea pig gastric fundus, were used to study the effects of H-1 and H-2 antagonists on acetylcholine (ACH)- and histamine (HA)-induced contractions as well as the effects of HA antagonists on spontaneous contractile activity. HA (1 times 10-9 M to 1 times 10-5 M) concentration-dependently enhanced the tone of the strips with ED-50 = 3.5 times 10-7 M. Applied 5 min before HA, the Hi antagonists (mepyramine, diphenhydramine, dimethpyrindene) and the H-2 blockers (ranitidine, cimetidine, roxatidine) reduced HA -induced contractions. HA in concentrations of 1 times 10-8 M to 1 times 10-7 M potentiated, and in higher concentrations (1 times 10-6 M to 1 times 10-5 M) inhibited, smooth muscle contractions evoked by low frequency electrical field stimulation (EFS). The H-1 blockers (1 times 10-6 M to 1 times 10-4 M) concentration-dependently enhanced smooth muscle tone, the maximum contractions being about 50% smaller than the contractile responses to 1 times 10-5 M ACH and 5 times 10-5 M HA. Tetrodotoxin, atropine and indomethacin shifted to the right the concentration-response curve for mepyramine, reducing its maximum by 25, 58 and 62%, respectively. The H-2 blacker ranitidine also suppressed (by 42%) mepyramine-evoked increase in the fundic strips tone. The H-1 antagonists reduced ACH-induced contractions of the smooth muscle strips and did not affect the contractions in response to EFS. The H-2 blockers had no effect on tone and ACH-evoked contractions of the smooth muscle strips but concentration-dependently enhanced both the contractions and (3H)-ACH release in response to EFS. The results demonstrate the presence 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 modulate the cholinergic neurotransmission in gastric fundus. It could be suggested that H-1 blockers have a direct myogenic effect on guinea pig gastric fundus smooth muscle and might also interact postsynaptically with muscarinic receptors in this tissue.
Document emailed within 1 workday
