5‐HT decreases contractile and electrical activities in lymphatic vessels of the guinea‐pig mesentery: role of 5‐HT7‐receptors
- 1 May 2003
- journal article
- Published by Wiley in British Journal of Pharmacology
- Vol. 139 (2) , 243-254
- https://doi.org/10.1038/sj.bjp.0705264
Abstract
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.Keywords
This publication has 53 references indexed in Scilit:
- Effects of histamine on the contractile and electrical activity in isolated lymphatic vessels of the guinea‐pig mesenteryBritish Journal of Pharmacology, 2002
- Pharmacological characterization of the 5‐HT receptors mediating contraction and relaxation of canine isolated proximal stomach smooth muscleBritish Journal of Pharmacology, 2002
- 5-HT Inhibits Spontaneous Contractility of Isolated Sheep Mesenteric Lymphatics via Activation of 5-HT4 ReceptorsMicrovascular Research, 2000
- A Novel, Potent, and Selective 5-HT7Antagonist: (R)-3-(2-(2-(4-Methylpiperidin-1-yl)ethyl)pyrrolidine-1-sulfonyl)phenol (SB-269970)Journal of Medicinal Chemistry, 2000
- Evidence for 5‐HT7 receptors mediating relaxation of human colonic circular smooth muscleBritish Journal of Pharmacology, 1999
- Evidence that the ATP‐induced increase in vasomotion of guinea‐pig mesenteric lymphatics involves an endothelium‐dependent release of thromboxane A2British Journal of Pharmacology, 1999
- ATP‐sensitive K+ channels in smooth muscle cells of guinea‐pig mesenteric lymphatics: role in nitric oxide and β‐adrenoceptor agonist‐induced hyperpolarizationsBritish Journal of Pharmacology, 1998
- Involvement of 5‐hydroxytryptamine7 receptors in inhibition of porcine myometrial contractility by 5‐hydroxytryptamineBritish Journal of Pharmacology, 1998
- Evidence that the substance P‐induced enhancement of pacemaking in lymphatics of the guinea‐pig mesentery occurs through endothelial release of thromboxane A2British Journal of Pharmacology, 1997
- Interaction of Inflammatory Mediators with the Lymphatic VesselPathology and Immunopathology Research, 1987