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Serotonin-induced contraction in porcine coronary artery: use of ergolines to support vascular 5-hydroxytryptamine2-receptor heterogeneity.
J Pharmacol Exp Ther. 1993 Jan; 264(1):193-200.JP

Abstract

Serotonin-induced contraction in porcine coronary artery was studied in ring segments of coronary artery without endothelium. 5-hydroxytryptamine (5-HT), 5-methoxytryptamine (5-MeOT) and alpha-methyl-5-HT (alpha Me-5-HT) concentration-dependently contracted vessels with similar maximal force. The agonist rank order potency was 5-HT > alpha Me-5-HT > 5-MeOT. Neither prazosin (1 microM) nor tetrodotoxin (0.3 microM) significantly altered 5-HT-induced contraction, ruling out activation of alpha-1 adrenoceptors and sodium channels in the contractile response, respectively. Using 5-MeOT as the prototype agonist, cyanopindolol blocked contraction with an antagonist dissociation constant lower than expected for 5-HT1-receptor blockade and ICS 205-930 (10 microM) did not affect 5-MeOT-induced contraction. Five structurally distinct 5-HT2-receptor antagonists (ketanserin, cisapride, spiperone, MDL11939, ICI169369) blocked 5-HT-induced contraction with antagonist dissociation constants similar to reported 5-HT2-receptor affinities. Two ergoline-based 5-HT2-receptor antagonists, LY53857 and sergolexole, blocked 5-HT-induced contraction with antagonist dissociation constants lower than expected for vascular 5-HT2-receptor blockade. Based on the agonist profile and the fact that ICS 205-930 and cyanopindolol were not potent antagonists, the 5-HT receptor-mediating contraction does not represent either the 5-HT1A/B/C/D, 5-HT3 or 5-HT4 receptor. Rather, based on the affinity of several established 5-HT2-receptor antagonists, a 5-HT2 receptor mediates contraction in porcine coronary artery. However, the low antagonist affinity of the ergolines (i.e., LY53857 and sergolexole) suggests that heterogeneity of 5-HT2 receptors may exist among species.

Authors+Show Affiliations

Cardiovascular Research, Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana.No affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

8423526

Citation

Cushing, D J., and M L. Cohen. "Serotonin-induced Contraction in Porcine Coronary Artery: Use of Ergolines to Support Vascular 5-hydroxytryptamine2-receptor Heterogeneity." The Journal of Pharmacology and Experimental Therapeutics, vol. 264, no. 1, 1993, pp. 193-200.
Cushing DJ, Cohen ML. Serotonin-induced contraction in porcine coronary artery: use of ergolines to support vascular 5-hydroxytryptamine2-receptor heterogeneity. J Pharmacol Exp Ther. 1993;264(1):193-200.
Cushing, D. J., & Cohen, M. L. (1993). Serotonin-induced contraction in porcine coronary artery: use of ergolines to support vascular 5-hydroxytryptamine2-receptor heterogeneity. The Journal of Pharmacology and Experimental Therapeutics, 264(1), 193-200.
Cushing DJ, Cohen ML. Serotonin-induced Contraction in Porcine Coronary Artery: Use of Ergolines to Support Vascular 5-hydroxytryptamine2-receptor Heterogeneity. J Pharmacol Exp Ther. 1993;264(1):193-200. PubMed PMID: 8423526.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Serotonin-induced contraction in porcine coronary artery: use of ergolines to support vascular 5-hydroxytryptamine2-receptor heterogeneity. AU - Cushing,D J, AU - Cohen,M L, PY - 1993/1/1/pubmed PY - 1993/1/1/medline PY - 1993/1/1/entrez SP - 193 EP - 200 JF - The Journal of pharmacology and experimental therapeutics JO - J Pharmacol Exp Ther VL - 264 IS - 1 N2 - Serotonin-induced contraction in porcine coronary artery was studied in ring segments of coronary artery without endothelium. 5-hydroxytryptamine (5-HT), 5-methoxytryptamine (5-MeOT) and alpha-methyl-5-HT (alpha Me-5-HT) concentration-dependently contracted vessels with similar maximal force. The agonist rank order potency was 5-HT > alpha Me-5-HT > 5-MeOT. Neither prazosin (1 microM) nor tetrodotoxin (0.3 microM) significantly altered 5-HT-induced contraction, ruling out activation of alpha-1 adrenoceptors and sodium channels in the contractile response, respectively. Using 5-MeOT as the prototype agonist, cyanopindolol blocked contraction with an antagonist dissociation constant lower than expected for 5-HT1-receptor blockade and ICS 205-930 (10 microM) did not affect 5-MeOT-induced contraction. Five structurally distinct 5-HT2-receptor antagonists (ketanserin, cisapride, spiperone, MDL11939, ICI169369) blocked 5-HT-induced contraction with antagonist dissociation constants similar to reported 5-HT2-receptor affinities. Two ergoline-based 5-HT2-receptor antagonists, LY53857 and sergolexole, blocked 5-HT-induced contraction with antagonist dissociation constants lower than expected for vascular 5-HT2-receptor blockade. Based on the agonist profile and the fact that ICS 205-930 and cyanopindolol were not potent antagonists, the 5-HT receptor-mediating contraction does not represent either the 5-HT1A/B/C/D, 5-HT3 or 5-HT4 receptor. Rather, based on the affinity of several established 5-HT2-receptor antagonists, a 5-HT2 receptor mediates contraction in porcine coronary artery. However, the low antagonist affinity of the ergolines (i.e., LY53857 and sergolexole) suggests that heterogeneity of 5-HT2 receptors may exist among species. SN - 0022-3565 UR - https://www.unboundmedicine.com/medline/citation/8423526/Serotonin_induced_contraction_in_porcine_coronary_artery:_use_of_ergolines_to_support_vascular_5_hydroxytryptamine2_receptor_heterogeneity_ L2 - https://jpet.aspetjournals.org/cgi/pmidlookup?view=long&pmid=8423526 DB - PRIME DP - Unbound Medicine ER -