5-HT decreases contractile and electrical activities in lymphatic vessels of the guinea-pig mesentery: role of 5-HT 7-receptors.
1 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. 2 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). 3 The actions of 5-HT were significantly reversed by the 5-HT(7) receptor antagonist (2R)-1-[(3-hydroxyphenyl)sulfonyl]-2-[2-(4-methyl-1-piperidinyl)ethyl]pyrrolidine (SB269970, 0.5 micro M) and by the 5-HT(1/2/5/7) receptor antagonists methysergide (0.5 micro M), and were mimicked by the 5-HT(1/7)-receptor agonist, 5-CT. 4 The 5-HT(4)-receptor antagonists 1-methyl-1H-indole-3-carboxylic acid [1-2-[(methyl sulfonyl) amino] ethyl-4-piperidinyl] methyl ester (GR113808, 1 micro M) and (1-piperidinyl) ethyl 1H-indole 3-carboxylate (SB203186, 1 micro 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 micro M and without affecting the smooth muscle membrane potential. 5 Responses to 5-HT were attenuated by the nitric oxide synthase inhibitor N(G)-nitro L-arginine (100 micro M), whereas indomethacin (10 micro M) and tetrodotoxin (1 micro M) were without effects. 6 5-HT-induced responses were inhibited by the ATP-sensitive K(+) channel blocker, glibenclamide (10 micro M) and the cAMP-dependent protein kinase inhibitor N-[2-(p-bromociannamylamino)-ethyl]-5-isoquinolinesulfonamide-dichloride (H89, 10 micro M) blocked the hyperpolarization. 7 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.
Chan
Alice K
AK
Mucosal Inflammation and Smooth Muscle Research Groups, Department of Physiology & Biophysics, Faculty of Medicine, University of Calgary, Canada.
von der Weid
Pierre-Yves
PY
D000818:Animals; D005260:Female; D005905:Glyburide / Q000494:pharmacology; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007546:Isoquinolines / Q000494:pharmacology; D042601:Lymphatic Vessels / Q000187:drug effects* / Q000502:physiology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D008643:Mesentery; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology; D015221:Potassium Channels / Q000502:physiology; D011985:Receptors, Serotonin / Q000187:drug effects* / Q000502:physiology; D012701:Serotonin / Q000494:pharmacology* / Q000502:physiology; D012702:Serotonin Antagonists / Q000494:pharmacology; D013449:Sulfonamides
D007546:Isoquinolines; D015221:Potassium Channels; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D013449:Sulfonamides; C104425:serotonin 7 receptor; D012701:Serotonin; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide; D005905:Glyburide