Adrenergic stimulation-released 5-HT stored in adrenergic nerves inhibits CGRPergic nerve-mediated vasodilatation in rat mesenteric resistance arteries

被引：11

作者：

Fujii, Hirohito ^{[1
]}

Takatori, Shingo ^{[1
]}

Zamami, Yoshito ^{[1
]}

Hashikawa-Hobara, Narumi ^{[2
]}

Miyake, Natsuki ^{[1
]}

Tangsucharit, Panot ^{[1
]}

Mio, Mitsunobu ^{[3
]}

Kawasaki, Hiromu ^{[1
]}

机构：

[1] Okayama Univ, Dept Clin Pharmaceut Sci, Grad Sch Med Dent & Pharmaceut Sci, Okayama 7008530, Japan

[2] Okayama Univ Sci, Dept Life Sci, Okayama, Japan

[3] Shujitsu Univ, Fac Pharmaceut Sci, Dept Pharmacol, Okayama, Japan

来源：

BRITISH JOURNAL OF PHARMACOLOGY | 2012年 / 166卷 / 07期

关键词：

adrenergic nerve; calcitonin gene-related peptide-containing nerves; 5-HT; perivascular nerve interaction; rat mesenteric artery; GENE-RELATED PEPTIDE; VASOCONSTRICTOR RESPONSE; 5-HYDROXYTRYPTAMINE; CGRP; NICOTINE; NEUROTRANSMITTER; NORADRENALINE; MODULATION; RECEPTORS; VESSELS;

D O I：

10.1111/j.1476-5381.2012.01935.x

中图分类号：

R9 [药学];

学科分类号：

100702 [药剂学];

摘要：

BACKGROUND AND PURPOSE 5-HT is taken up by and stored in adrenergic nerves and periarterial nerve stimulation (PNS) releases 5-HT to cause vasoconstriction in rat mesenteric arteries. The present study investigated whether PNS-released 5-HT stored in adrenergic nerves affects the function of perivascular calcitonin gene-related peptide-containing (CGRPergic) nerves. EXPERIMENTAL APPROACH Rat mesenteric vascular beds without endothelium and with active tone were perfused with Krebs solution. Changes in perfusion pressure in response to PNS and CGRP injection were measured before (control) and after perfusion of Krebs solution containing 5-HT (10 mu M) for 20 min. Distributions of 5-HT- and TH-immunopositive fibres in mesenteric arteries were studied using immunohistochemical methods. KEY RESULTS PNS (14 Hz) frequency dependently caused adrenergic nerve-mediated vasoconstriction followed by CGRPergic nerve-mediated vasodilatation. 5-HT treatment inhibited PNS-induced vasodilatation without affecting exogenous CGRP-induced vasodilatation, while it augmented PNS-induced vasoconstriction. Guanethidine (adrenergic neuron blocker), methysergide (non-selective 5-HT receptor antagonist) and BRL15572 (selective 5-HT1D receptor antagonist) abolished inhibition of PNS-induced vasodilatation in 5-HT-treated preparations. Combined treatment with 5-HT and desipramine (catecholamine transporter inhibitor), but not fluoxetine (selective 5-HT reuptake inhibitor), did not inhibit PNS-induced vasodilatation. Exogenous 5-HT inhibited PNS-induced vasodilatation, which was antagonized by methysergide. In immunohistochemical experiments, 5-HT-immunopositive nerves, colocalized with adrenergic TH-immunopositive nerves, were observed only in 5-HT-treated mesenteric arteries, but not in control preparations or arteries co-treated with desipramine. CONCLUSIONS AND IMPLICATIONS These results suggest that 5-HT can be taken up by and released from adrenergic nerves in vitro by PNS to inhibit CGRPergic nerve transmission in rat mesenteric arteries.

引用

页码：2084 / 2094

页数：11

共 15 条

[1]

Activation of the 5-HT1B/D receptor reduces hindlimb neurogenic inflammation caused by sensory nerve stimulation and capsaicin [J].