Protons modulate perivascular axo-axonal neurotransmission in the rat mesenteric artery |
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Authors: | Shingo Takatori Kazuhiro Hirai Shuichiro Ozaki Panot Tangsucharit Satoko Fukushima-Miyashita Mitsuhiro Goda Narumi Hashikawa-Hobara Nobufumi Ono Hiromu Kawasaki |
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Affiliation: | 1.Department of Clinical Pharmacy, College of Pharmaceutical Sciences, Matsuyama University, Matsuyama, Ehime, Japan;2.Department of Clinical Pharmaceutical Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan;3.Department of Life Science, Okayama University of Science, Kita-ku, Okayama, Japan;4.Department of Drug Information, Faculty of Pharmaceutical Sciences, Fukuoka University, Fukuoka, Japan |
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Abstract: | Background and PurposePrevious studies have demonstrated that nicotine releases protons from adrenergic nerves via stimulation of nicotinic ACh receptors and activates transient receptor potential vanilloid-1 (TRPV1) receptors located on calcitonin gene-related peptide (CGRP)-containing (CGRPergic) vasodilator nerves, resulting in vasodilatation. The present study investigated whether perivascular nerves release protons, which modulate axon-axonal neurotransmission.Experiment ApproachPerfusion pressure and pH levels of perfusate in rat-perfused mesenteric vascular beds without endothelium were measured with a pressure transducer and a pH meter respectively.Key ResultsPeriarterial nerve stimulation (PNS) initially induced vasoconstriction, which was followed by long-lasting vasodilatation and decreased pH levels in the perfusate. Cold-storage denervation of the preparation abolished the decreased pH and vascular responses to PNS. The adrenergic neuron blocker guanethidine inhibited PNS-induced vasoconstriction and effects on pH, but not PNS-induced vasodilatation. Capsaicin (CGRP depletor), capsazepine and ruthenium red (TRPV1 inhibitors) attenuated the PNS-induced decrease in pH and vasodilatation. In denuded preparations, ACh caused long-lasting vasodilatation and lowered pH; these effects were inhibited by capsaicin pretreatment and atropine, but not by guanethidine or mecamylamine. Capsaicin injection induced vasodilatation and a reduction in pH, which were abolished by ruthenium red. The use of a fluorescent pH indicator demonstrated that application of nicotine, ACh and capsaicin outside small mesenteric arteries reduced perivascular pH levels and these effects were abolished in a Ca2+-free medium.Conclusion and ImplicationThese results suggest that protons are released from perivascular adrenergic and CGRPergic nerves upon PNS and these protons modulate transmission in CGRPergic nerves.Tables of LinksTargets |
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GPCRs | α1-adrenoceptor | Muscarinic ACh receptor | CGRP receptor | Ligand-gated ion channels | Nicotinic ACh receptor | Ion channels | TRPV1 channel | Open in a separate windowLIGANDS | |
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ACh | Mecamylamine | Atropine | Methoxamine | Capsaicin | Neuropeptide Y | Capsazepine | Nicotine | CGRP | Nitric oxide (NO) | Guanethidine | Noradrenaline | | Ruthenium red | Open in a separate windowThese Tables list key protein targets and ligands in this article which are hyperlinked to corresponding entries in http://www.guidetopharmacology.org, the common portal for data from the IUPHAR/BPS Guide to PHARMACOLOGY (Pawson et al., 2014) and are permanently archived in the Concise Guide to PHARMACOLOGY 2013/14 (Alexander et al., 2013a,b,c,,). |
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