Serotonin receptors in rat jugular vein: presence and involvement in the contraction.
Serotonin (5-hydroxytryptamine; 5-HT) is released during platelet aggregation, a phenomenon commonly observed in blood clot formation and venous diseases. Once released, 5-HT can interact with its receptors in the peripheral vasculature to modify vascular tone. The goal of this study was to perform a detailed pharmacological characterization of the 5-HT receptors involved in the contractile response of the rat jugular vein (RJV) using recently developed drugs with greater selectivity toward 5-HT receptor subtypes. We hypothesized that, as for other blood vessels, the 5-HT(1B/1D) and 5-HT(2B) receptor subtypes mediate contraction in RJV alongside the 5-HT(2A) receptor subtype. Endothelium-intact RJV rings were set up in an isolated organ bath for isometric tension recordings, and contractile concentration-effect curves were obtained for 13 distinct serotonergic receptor agonists. Surprisingly, the 5-HT(1A) and the mixed 5-HT(1A/1B) receptor agonists (+/-)-2-dipropyl-amino-8-hydroxyl-1,2,3,4-tetrahydronapthalene (8-OH-DPAT) and 5-methoxy-3 (1,2,3,6-tetrahydropyridin-4-yl) (1H indole) (RU24969) caused contractions that were antagonized by the 5-HT(1A) receptor antagonist [O-methyl-3H]-N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide (WAY100135). The contractile curve to 5-HT was shifted to the right by WAY100135, 3-[2-[4-(4-fluoro benzoyl)-piperidin-1-yl]ethyl]-1H-quinazoline-2,4-dione (ketanserin; 5-HT(2A/C) receptor antagonist), and 1-(2-chloro-3,4-dimethoxybenzyl)-6-methyl-1,2,3,4-tetrahydro-9H-pyrido[3,4-b]indole hydrochloride (LY266097; 5-HT(2B) receptor antagonist). Ketanserin also caused rightward shifts of the contractile curves to 8-OH-DPAT, RU24969, and the 5-HT(2B) receptor agonist (alpha-methyl-5-(2-thienylmethoxy)-1H-indole-3-ethanamine) (BW723C86). Agonists for 5-HT(1B/1D/1F), 5-HT(3), 5-HT(6), and 5-HT(7) receptors were inactive. In real-time polymerase chain reaction experiments that have never been performed in this tissue previously, we observed mRNA expression for the 5-HT(2A), 5-HT(2B), and 5-HT(7) receptors, whereas no significant mRNA expression was found for 5-HT(1A), 5-HT(1B), and 5-HT(1D) receptors. These results support the 5-HT(2A) receptor as the main subtype targeted by 5-HT to contract the RJV.
Linder
A Elizabeth
AE
Department of Pharmacology and Toxicology, Michigan State University, East Lansing, Michigan, USA. beth.linder@ccb.ufsc.br
Gaskell
Geri L
GL
Szasz
Theodora
T
Thompson
Janice M
JM
Watts
Stephanie W
SW
D000818:Animals; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D066298:In Vitro Techniques; D007601:Jugular Veins / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011985:Receptors, Serotonin / Q000096:biosynthesis / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012702:Serotonin Antagonists / Q000494:pharmacology*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*
D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists