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Involvement of 5-hydroxytryptamine7 receptors in inhibition of porcine myometrial contractility by 5-hydroxytryptamine.
Br J Pharmacol. 1998 Jan; 123(2):173-82.BJ

Abstract

1 5-Hydroxytryptamine (5-HT; 1 nM - 100 microM) concentration-dependently inhibited the amplitude and frequency of spontaneous contractions in longitudinal and circular muscles of the porcine myometrium. The circular muscle (EC50; 68-84 nM) was more sensitive than the longitudinal muscle (EC50; 1.3-1.44 microM) to 5-HT. To characterize the 5-HT receptor subtype responsible for inhibition of myometrial contractility, the effects of 5-HT receptor agonists on spontaneous contractions and of 5-HT receptor antagonists on inhibition by 5-HT were examined in circular muscle preparations. 2 Pretreatment with tetrodotoxin (1 microM), propranolol (1 microM), atropine (1 microM), guanethidine (10 microM) or L-NAME (100 microM) failed to change the inhibition by 5-HT, indicating that the inhibition was due to a direct action of 5-HT on the smooth muscle cells. 3 5-CT, 5-MeOT and 8-OH-DPAT mimicked the inhibitory response of 5-HT, and the rank order of the potency was 5-CT>5-HT>5-MeOT>8-OH-DPAT. On the other hand, oxymethazoline, alpha-methyl-5-HT, 2-methyl-5-HT, cisapride, BIMU-1, BIMU-8, ergotamine and dihydroergotamine had almost no effect on spontaneous contractions, even at 10-100 microM. 4 Inhibition by 5-HT was not decreased by either pindolol (1 microM), ketanserin (1 microM), tropisetron (10 microM), MDL72222 (1 microM) or GR113808 (10 microM), but was antagonized by the following compounds in a competitive manner (with pA2 values in parentheses): methiothepin (8.05), methysergide (7.92), metergoline (7.4), mianserin (7.08), clozapine (7.06) and spiperone (6.86). 5 Ro 20-1724 (20 microM) and rolipram (10 microM) significantly enhanced the inhibitory response of 5-HT, but neither zaprinast (10 microM) nor dipyridamole (10 microM) altered the response of 5-HT. 6 5-HT (1 nM - 1 microM) caused a concentration-dependent accumulation of intracellular cyclic AMP in the circular muscle. 7 From the present results, the 5-HT receptor, which is functionally correlated with the 5-HT7 receptor, mediates the inhibitory effect of 5-HT on porcine myometrial contractility. This inhibitory response is probably due to an increase in intracellular cyclic AMP through the activation of adenylate cyclase that is positively coupled to 5-HT7 receptors.

Authors+Show Affiliations

Department of Pharmacology, Faculty of Veterinary Medicine, Rakuno Gakuen University, Ebetsu, Hokkaido, Japan.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

9489604

Citation

Kitazawa, T, et al. "Involvement of 5-hydroxytryptamine7 Receptors in Inhibition of Porcine Myometrial Contractility By 5-hydroxytryptamine." British Journal of Pharmacology, vol. 123, no. 2, 1998, pp. 173-82.
Kitazawa T, Kubo O, Satoh M, et al. Involvement of 5-hydroxytryptamine7 receptors in inhibition of porcine myometrial contractility by 5-hydroxytryptamine. Br J Pharmacol. 1998;123(2):173-82.
Kitazawa, T., Kubo, O., Satoh, M., & Taneike, T. (1998). Involvement of 5-hydroxytryptamine7 receptors in inhibition of porcine myometrial contractility by 5-hydroxytryptamine. British Journal of Pharmacology, 123(2), 173-82.
Kitazawa T, et al. Involvement of 5-hydroxytryptamine7 Receptors in Inhibition of Porcine Myometrial Contractility By 5-hydroxytryptamine. Br J Pharmacol. 1998;123(2):173-82. PubMed PMID: 9489604.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Involvement of 5-hydroxytryptamine7 receptors in inhibition of porcine myometrial contractility by 5-hydroxytryptamine. AU - Kitazawa,T, AU - Kubo,O, AU - Satoh,M, AU - Taneike,T, PY - 1998/3/7/pubmed PY - 1998/3/7/medline PY - 1998/3/7/entrez SP - 173 EP - 82 JF - British journal of pharmacology JO - Br J Pharmacol VL - 123 IS - 2 N2 - 1 5-Hydroxytryptamine (5-HT; 1 nM - 100 microM) concentration-dependently inhibited the amplitude and frequency of spontaneous contractions in longitudinal and circular muscles of the porcine myometrium. The circular muscle (EC50; 68-84 nM) was more sensitive than the longitudinal muscle (EC50; 1.3-1.44 microM) to 5-HT. To characterize the 5-HT receptor subtype responsible for inhibition of myometrial contractility, the effects of 5-HT receptor agonists on spontaneous contractions and of 5-HT receptor antagonists on inhibition by 5-HT were examined in circular muscle preparations. 2 Pretreatment with tetrodotoxin (1 microM), propranolol (1 microM), atropine (1 microM), guanethidine (10 microM) or L-NAME (100 microM) failed to change the inhibition by 5-HT, indicating that the inhibition was due to a direct action of 5-HT on the smooth muscle cells. 3 5-CT, 5-MeOT and 8-OH-DPAT mimicked the inhibitory response of 5-HT, and the rank order of the potency was 5-CT>5-HT>5-MeOT>8-OH-DPAT. On the other hand, oxymethazoline, alpha-methyl-5-HT, 2-methyl-5-HT, cisapride, BIMU-1, BIMU-8, ergotamine and dihydroergotamine had almost no effect on spontaneous contractions, even at 10-100 microM. 4 Inhibition by 5-HT was not decreased by either pindolol (1 microM), ketanserin (1 microM), tropisetron (10 microM), MDL72222 (1 microM) or GR113808 (10 microM), but was antagonized by the following compounds in a competitive manner (with pA2 values in parentheses): methiothepin (8.05), methysergide (7.92), metergoline (7.4), mianserin (7.08), clozapine (7.06) and spiperone (6.86). 5 Ro 20-1724 (20 microM) and rolipram (10 microM) significantly enhanced the inhibitory response of 5-HT, but neither zaprinast (10 microM) nor dipyridamole (10 microM) altered the response of 5-HT. 6 5-HT (1 nM - 1 microM) caused a concentration-dependent accumulation of intracellular cyclic AMP in the circular muscle. 7 From the present results, the 5-HT receptor, which is functionally correlated with the 5-HT7 receptor, mediates the inhibitory effect of 5-HT on porcine myometrial contractility. This inhibitory response is probably due to an increase in intracellular cyclic AMP through the activation of adenylate cyclase that is positively coupled to 5-HT7 receptors. SN - 0007-1188 UR - https://www.unboundmedicine.com/medline/citation/9489604/Involvement_of_5_hydroxytryptamine7_receptors_in_inhibition_of_porcine_myometrial_contractility_by_5_hydroxytryptamine_ L2 - https://doi.org/10.1038/sj.bjp.0701583 DB - PRIME DP - Unbound Medicine ER -