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Interactions between histaminergic and cholinergic pathways of gastric motility regulation.
Methods Find Exp Clin Pharmacol. 1996 Jan-Feb; 18(1):33-9.MF

Abstract

Smooth muscle preparations, isolated in a circular direction from guinea pig gastric fundus, were used to study the effects of H1 and H2 antagonists on acetylcholine (ACH)- and histamine (HA)-induced contractions as well as the effects of HA antagonists on spontaneous contractile activity. HA (1 x 10(-9) M to 1 x 10(-5) M) concentration-dependently enhanced the tone of the strips with ED50 = 3.5 x 10(-7) M. Applied 5 min before HA, the H1 antagonists (mepyramine, diphenhydramine, dimethpyrindene) and the H2 blockers (ranitidine, cimetidine, roxatidine) reduced HA-induced contractions. HA in concentrations of 1 x 10(-8) M to 1 x 10(-7) 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 H1 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 the contractile responses to 1 x 10(-5) M ACH and 5 x 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 H2 blocker ranitidine also suppressed (by 42%) mepyramine-evoked increase in the fundic strips tone. The H1 antagonists reduced ACH-induced contractions of the smooth muscle strips and did not affect the contractions in response to EFS. The H2 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 H1 and H2 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 H1 blockers have a direct myogenic effect on guinea pig gastric fundus smooth muscle and might also interact postsynaptically with muscarinic receptors in this tissue.

Authors+Show Affiliations

Institute of Physiology, Bulgarian Academy of Sciences, Sofia.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

8721254

Citation

Milenov, K, et al. "Interactions Between Histaminergic and Cholinergic Pathways of Gastric Motility Regulation." Methods and Findings in Experimental and Clinical Pharmacology, vol. 18, no. 1, 1996, pp. 33-9.
Milenov K, Todorov S, Vassileva M, et al. Interactions between histaminergic and cholinergic pathways of gastric motility regulation. Methods Find Exp Clin Pharmacol. 1996;18(1):33-9.
Milenov, K., Todorov, S., Vassileva, M., Zamfirova, R., & Shahbazian, A. (1996). Interactions between histaminergic and cholinergic pathways of gastric motility regulation. Methods and Findings in Experimental and Clinical Pharmacology, 18(1), 33-9.
Milenov K, et al. Interactions Between Histaminergic and Cholinergic Pathways of Gastric Motility Regulation. Methods Find Exp Clin Pharmacol. 1996 Jan-Feb;18(1):33-9. PubMed PMID: 8721254.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Interactions between histaminergic and cholinergic pathways of gastric motility regulation. AU - Milenov,K, AU - Todorov,S, AU - Vassileva,M, AU - Zamfirova,R, AU - Shahbazian,A, PY - 1996/1/1/pubmed PY - 1996/1/1/medline PY - 1996/1/1/entrez SP - 33 EP - 9 JF - Methods and findings in experimental and clinical pharmacology JO - Methods Find Exp Clin Pharmacol VL - 18 IS - 1 N2 - Smooth muscle preparations, isolated in a circular direction from guinea pig gastric fundus, were used to study the effects of H1 and H2 antagonists on acetylcholine (ACH)- and histamine (HA)-induced contractions as well as the effects of HA antagonists on spontaneous contractile activity. HA (1 x 10(-9) M to 1 x 10(-5) M) concentration-dependently enhanced the tone of the strips with ED50 = 3.5 x 10(-7) M. Applied 5 min before HA, the H1 antagonists (mepyramine, diphenhydramine, dimethpyrindene) and the H2 blockers (ranitidine, cimetidine, roxatidine) reduced HA-induced contractions. HA in concentrations of 1 x 10(-8) M to 1 x 10(-7) 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 H1 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 the contractile responses to 1 x 10(-5) M ACH and 5 x 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 H2 blocker ranitidine also suppressed (by 42%) mepyramine-evoked increase in the fundic strips tone. The H1 antagonists reduced ACH-induced contractions of the smooth muscle strips and did not affect the contractions in response to EFS. The H2 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 H1 and H2 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 H1 blockers have a direct myogenic effect on guinea pig gastric fundus smooth muscle and might also interact postsynaptically with muscarinic receptors in this tissue. SN - 0379-0355 UR - https://www.unboundmedicine.com/medline/citation/8721254/Interactions_between_histaminergic_and_cholinergic_pathways_of_gastric_motility_regulation_ DB - PRIME DP - Unbound Medicine ER -