α3β4-Nicotinic receptors mediate adrenergic nerve- and peptidergic (CGRP) nerve-dependent vasodilation induced by nicotine in rat mesenteric arteries

S. Eguchi, S. Miyashita, Yoshihisa Kitamura, H. Kawasaki

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

Background and purpose: Previous studies demonstrated that nicotine-induced endothelium-independent vasodilation is mediated by perivascular adrenergic nerves and nerves releasing calcitonin gene-related peptide (CGRPergic nerves). We characterized the nicotinic acetylcholine (ACh) receptor subtype underlying the vasodilation in response to nicotine in rat mesenteric arteries. Experimental approach: Rat mesenteric vascular beds without endothelium were contracted by perfusion with Krebs solution containing methoxamine and the perfusion pressure was measured with a pressure transducer. Key results: Perfusion of nicotine (1-100 μM) for 1 min caused a concentration-dependent decrease in perfusion pressure due to vasodilation. Perfusion of (±)-epibatidine (1-100 nM) (non-selective agonist) or (-)-cytisine (1-100 μM) (partial agonist for nicotinic β2 subtype and full agonist for nicotinic β4 subtype) induced vasodilation in a concentration-dependent manner. Vasodilation induced by nicotine, (-)-cytisine- and (±)- epibatidine was markedly attenuated by guanethidine (5 μM) and pretreatment with capsaicin (1 μM). Mecamylamine (relatively selective antagonist for α3β4 subtype), but not dihydro-β-erythroidine (selective antagonist for α4β2 subtype) or α-bungarotoxin (selective antagonist for α7 subtype), markedly inhibited nicotine-induced vasodilation. Nicotine-induced vasodilation was inhibited by methyllycaconitine at high concentrations (>1 μM), which non-selectively antagonize nicotinic receptors, while a low concentration of 10 nM, which selectively antagonizes α7 subtype, had no effect. (-)-Cytisine and (±)-epibatidine-induced vasodilation were abolished by mecamylamine Conclusion and implications: These results suggest that the nicotinic α3β4 receptor subtype, but not the α7 and α4β2 subtypes, is responsible for the vasodilation in rat mesenteric arteries induced by nicotine- and nicotinic ACh receptor agonists through stimulation of adrenergic and CGRPergic perivascular nerves.

Original languageEnglish
Pages (from-to)1216-1223
Number of pages8
JournalBritish Journal of Pharmacology
Volume151
Issue number8
DOIs
Publication statusPublished - Aug 2007

Fingerprint

Mesenteric Arteries
Nicotinic Receptors
Nicotine
Vasodilation
Adrenergic Agents
epibatidine
Perfusion
Nicotinic Agonists
Mecamylamine
Endothelium
Methoxamine
Pressure Transducers
Guanethidine
Pressure
Bungarotoxins
Cholinergic Agonists
Calcitonin Gene-Related Peptide
Capsaicin
Blood Vessels

Keywords

  • α3β4 nicotinic receptor subtype
  • Adrenergic nerves
  • Calcitonin gene-related peptide-containing nerves
  • Nicotine
  • Rat mesenteric resistance artery
  • Vasodilation

ASJC Scopus subject areas

  • Pharmacology

Cite this

α3β4-Nicotinic receptors mediate adrenergic nerve- and peptidergic (CGRP) nerve-dependent vasodilation induced by nicotine in rat mesenteric arteries. / Eguchi, S.; Miyashita, S.; Kitamura, Yoshihisa; Kawasaki, H.

In: British Journal of Pharmacology, Vol. 151, No. 8, 08.2007, p. 1216-1223.

Research output: Contribution to journalArticle

@article{838428a1eb3342c291fde7f3c12b9f1e,
title = "α3β4-Nicotinic receptors mediate adrenergic nerve- and peptidergic (CGRP) nerve-dependent vasodilation induced by nicotine in rat mesenteric arteries",
abstract = "Background and purpose: Previous studies demonstrated that nicotine-induced endothelium-independent vasodilation is mediated by perivascular adrenergic nerves and nerves releasing calcitonin gene-related peptide (CGRPergic nerves). We characterized the nicotinic acetylcholine (ACh) receptor subtype underlying the vasodilation in response to nicotine in rat mesenteric arteries. Experimental approach: Rat mesenteric vascular beds without endothelium were contracted by perfusion with Krebs solution containing methoxamine and the perfusion pressure was measured with a pressure transducer. Key results: Perfusion of nicotine (1-100 μM) for 1 min caused a concentration-dependent decrease in perfusion pressure due to vasodilation. Perfusion of (±)-epibatidine (1-100 nM) (non-selective agonist) or (-)-cytisine (1-100 μM) (partial agonist for nicotinic β2 subtype and full agonist for nicotinic β4 subtype) induced vasodilation in a concentration-dependent manner. Vasodilation induced by nicotine, (-)-cytisine- and (±)- epibatidine was markedly attenuated by guanethidine (5 μM) and pretreatment with capsaicin (1 μM). Mecamylamine (relatively selective antagonist for α3β4 subtype), but not dihydro-β-erythroidine (selective antagonist for α4β2 subtype) or α-bungarotoxin (selective antagonist for α7 subtype), markedly inhibited nicotine-induced vasodilation. Nicotine-induced vasodilation was inhibited by methyllycaconitine at high concentrations (>1 μM), which non-selectively antagonize nicotinic receptors, while a low concentration of 10 nM, which selectively antagonizes α7 subtype, had no effect. (-)-Cytisine and (±)-epibatidine-induced vasodilation were abolished by mecamylamine Conclusion and implications: These results suggest that the nicotinic α3β4 receptor subtype, but not the α7 and α4β2 subtypes, is responsible for the vasodilation in rat mesenteric arteries induced by nicotine- and nicotinic ACh receptor agonists through stimulation of adrenergic and CGRPergic perivascular nerves.",
keywords = "α3β4 nicotinic receptor subtype, Adrenergic nerves, Calcitonin gene-related peptide-containing nerves, Nicotine, Rat mesenteric resistance artery, Vasodilation",
author = "S. Eguchi and S. Miyashita and Yoshihisa Kitamura and H. Kawasaki",
year = "2007",
month = "8",
doi = "10.1038/sj.bjp.0707331",
language = "English",
volume = "151",
pages = "1216--1223",
journal = "British Journal of Pharmacology",
issn = "0007-1188",
publisher = "Wiley-Blackwell",
number = "8",

}

TY - JOUR

T1 - α3β4-Nicotinic receptors mediate adrenergic nerve- and peptidergic (CGRP) nerve-dependent vasodilation induced by nicotine in rat mesenteric arteries

AU - Eguchi, S.

AU - Miyashita, S.

AU - Kitamura, Yoshihisa

AU - Kawasaki, H.

PY - 2007/8

Y1 - 2007/8

N2 - Background and purpose: Previous studies demonstrated that nicotine-induced endothelium-independent vasodilation is mediated by perivascular adrenergic nerves and nerves releasing calcitonin gene-related peptide (CGRPergic nerves). We characterized the nicotinic acetylcholine (ACh) receptor subtype underlying the vasodilation in response to nicotine in rat mesenteric arteries. Experimental approach: Rat mesenteric vascular beds without endothelium were contracted by perfusion with Krebs solution containing methoxamine and the perfusion pressure was measured with a pressure transducer. Key results: Perfusion of nicotine (1-100 μM) for 1 min caused a concentration-dependent decrease in perfusion pressure due to vasodilation. Perfusion of (±)-epibatidine (1-100 nM) (non-selective agonist) or (-)-cytisine (1-100 μM) (partial agonist for nicotinic β2 subtype and full agonist for nicotinic β4 subtype) induced vasodilation in a concentration-dependent manner. Vasodilation induced by nicotine, (-)-cytisine- and (±)- epibatidine was markedly attenuated by guanethidine (5 μM) and pretreatment with capsaicin (1 μM). Mecamylamine (relatively selective antagonist for α3β4 subtype), but not dihydro-β-erythroidine (selective antagonist for α4β2 subtype) or α-bungarotoxin (selective antagonist for α7 subtype), markedly inhibited nicotine-induced vasodilation. Nicotine-induced vasodilation was inhibited by methyllycaconitine at high concentrations (>1 μM), which non-selectively antagonize nicotinic receptors, while a low concentration of 10 nM, which selectively antagonizes α7 subtype, had no effect. (-)-Cytisine and (±)-epibatidine-induced vasodilation were abolished by mecamylamine Conclusion and implications: These results suggest that the nicotinic α3β4 receptor subtype, but not the α7 and α4β2 subtypes, is responsible for the vasodilation in rat mesenteric arteries induced by nicotine- and nicotinic ACh receptor agonists through stimulation of adrenergic and CGRPergic perivascular nerves.

AB - Background and purpose: Previous studies demonstrated that nicotine-induced endothelium-independent vasodilation is mediated by perivascular adrenergic nerves and nerves releasing calcitonin gene-related peptide (CGRPergic nerves). We characterized the nicotinic acetylcholine (ACh) receptor subtype underlying the vasodilation in response to nicotine in rat mesenteric arteries. Experimental approach: Rat mesenteric vascular beds without endothelium were contracted by perfusion with Krebs solution containing methoxamine and the perfusion pressure was measured with a pressure transducer. Key results: Perfusion of nicotine (1-100 μM) for 1 min caused a concentration-dependent decrease in perfusion pressure due to vasodilation. Perfusion of (±)-epibatidine (1-100 nM) (non-selective agonist) or (-)-cytisine (1-100 μM) (partial agonist for nicotinic β2 subtype and full agonist for nicotinic β4 subtype) induced vasodilation in a concentration-dependent manner. Vasodilation induced by nicotine, (-)-cytisine- and (±)- epibatidine was markedly attenuated by guanethidine (5 μM) and pretreatment with capsaicin (1 μM). Mecamylamine (relatively selective antagonist for α3β4 subtype), but not dihydro-β-erythroidine (selective antagonist for α4β2 subtype) or α-bungarotoxin (selective antagonist for α7 subtype), markedly inhibited nicotine-induced vasodilation. Nicotine-induced vasodilation was inhibited by methyllycaconitine at high concentrations (>1 μM), which non-selectively antagonize nicotinic receptors, while a low concentration of 10 nM, which selectively antagonizes α7 subtype, had no effect. (-)-Cytisine and (±)-epibatidine-induced vasodilation were abolished by mecamylamine Conclusion and implications: These results suggest that the nicotinic α3β4 receptor subtype, but not the α7 and α4β2 subtypes, is responsible for the vasodilation in rat mesenteric arteries induced by nicotine- and nicotinic ACh receptor agonists through stimulation of adrenergic and CGRPergic perivascular nerves.

KW - α3β4 nicotinic receptor subtype

KW - Adrenergic nerves

KW - Calcitonin gene-related peptide-containing nerves

KW - Nicotine

KW - Rat mesenteric resistance artery

KW - Vasodilation

UR - http://www.scopus.com/inward/record.url?scp=34547897347&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=34547897347&partnerID=8YFLogxK

U2 - 10.1038/sj.bjp.0707331

DO - 10.1038/sj.bjp.0707331

M3 - Article

VL - 151

SP - 1216

EP - 1223

JO - British Journal of Pharmacology

JF - British Journal of Pharmacology

SN - 0007-1188

IS - 8

ER -