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5‐HT decreases contractile and electrical activities in lymphatic vessels of the guinea‐pig mesentery: role of 5‐HT 7 ‐receptors
Author(s) -
Chan Alice K,
Der Weid PierreYves
Publication year - 2003
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0705264
Subject(s) - methysergide , agonist , 5 ht receptor , chemistry , receptor , receptor antagonist , vascular smooth muscle , serotonin , pharmacology , endocrinology , medicine , biophysics , antagonist , biochemistry , biology , smooth muscle
Constriction measurements and intracellular microelectrode recordings were performed in vitro on lymphatic vessels isolated from the guinea‐pig mesentery to investigate whether 5‐hydroxytryptamine (5‐HT) affected lymphatic pumping and smooth muscle membrane potential. 5‐HT decreased in a concentration‐dependent manner the frequency of constrictions induced by intraluminal vessel perfusion. In nonperfused vessels, 5‐HT hyperpolarized the lymphatic smooth muscle membrane potential and decreased the frequency and amplitude of spontaneous transient depolarizations (STDs). The actions of 5‐HT were significantly reversed by the 5‐HT 7 receptor antagonist (2 R )‐1‐[(3‐hydroxyphenyl)sulfonyl]‐2‐[2‐(4‐methyl‐1‐piperidinyl)ethyl]pyrrolidine (SB269970, 0.5 μ M ) and by the 5‐HT 1/2/5/7 receptor antagonists methysergide (0.5 μ M ), and were mimicked by the 5‐HT 1/7 ‐receptor agonist, 5‐CT. The 5‐HT 4 ‐receptor antagonists 1‐methyl‐1 H ‐indole‐3‐carboxylic acid [1‐2‐[(methyl sulfonyl) amino] ethyl‐4‐piperidinyl] methyl ester (GR113808, 1 μ M ) and (1‐piperidinyl) ethyl 1 H ‐indole 3‐carboxylate (SB203186, 1 μ M ) did not significantly affect the 5‐HT‐induced responses. The 5‐HT 4 ‐receptor agonist 1‐(4‐amino‐5‐chloro‐2‐methoxy‐phenyl)‐3‐[1‐(2‐methylsulfonylamino) ethyl‐4‐piperidinyl]‐1‐propanone hydrochloride (RS67506) decreased the constriction frequency, albeit only at 50 μ M and without affecting the smooth muscle membrane potential. Responses to 5‐HT were attenuated by the nitric oxide synthase inhibitor N G ‐nitro L ‐arginine (100 μ M ), whereas indomethacin (10 μ M ) and tetrodotoxin (1 μ M ) were without effects. 5‐HT‐induced responses were inhibited by the ATP‐sensitive K + channel blocker, glibenclamide (10 μ M ) and the cAMP‐dependent protein kinase inhibitor N ‐[2‐( p ‐bromociannamylamino)‐ethyl]‐5‐isoquinolinesulfonamide‐dichloride (H89, 10 μ M ) blocked the hyperpolarization. These results suggest that 5‐HT modulates the rate of lymphatic vessel pumping by eliciting K ATP channel‐mediated smooth muscle hyperpolarization and decrease in STD activity, which appear to be mediated by activation of 5‐HT 7 receptors coupled to cAMP production.British Journal of Pharmacology (2003) 139 , 243–254. doi: 10.1038/sj.bjp.0705264