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 language | English |
|---|---|
| Pages (from-to) | 1216-1223 |
| Number of pages | 8 |
| Journal | British Journal of Pharmacology |
| Volume | 151 |
| Issue number | 8 |
| DOIs | |
| Publication status | Published - Aug 2007 |
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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 journal › Article
}
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
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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 -