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Protons modulate perivascular axo-axonal neurotransmission in the rat mesenteric artery.
Br J Pharmacol. 2014 Dec; 171(24):5743-56.BJ

Abstract

BACKGROUND AND PURPOSE

Previous 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 APPROACH

Perfusion 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 RESULTS

Periarterial 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 Ca(2+) -free medium.

CONCLUSION AND IMPLICATION

These results suggest that protons are released from perivascular adrenergic and CGRPergic nerves upon PNS and these protons modulate transmission in CGRPergic nerves.

Authors+Show Affiliations

Department of Clinical Pharmacy, College of Pharmaceutical Sciences, Matsuyama University, Matsuyama, Ehime, Japan; Department of Clinical Pharmaceutical Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

25117291

Citation

Takatori, Shingo, et al. "Protons Modulate Perivascular Axo-axonal Neurotransmission in the Rat Mesenteric Artery." British Journal of Pharmacology, vol. 171, no. 24, 2014, pp. 5743-56.
Takatori S, Hirai K, Ozaki S, et al. Protons modulate perivascular axo-axonal neurotransmission in the rat mesenteric artery. Br J Pharmacol. 2014;171(24):5743-56.
Takatori, S., Hirai, K., Ozaki, S., Tangsucharit, P., Fukushima-Miyashita, S., Goda, M., Hashikawa-Hobara, N., Ono, N., & Kawasaki, H. (2014). Protons modulate perivascular axo-axonal neurotransmission in the rat mesenteric artery. British Journal of Pharmacology, 171(24), 5743-56. https://doi.org/10.1111/bph.12878
Takatori S, et al. Protons Modulate Perivascular Axo-axonal Neurotransmission in the Rat Mesenteric Artery. Br J Pharmacol. 2014;171(24):5743-56. PubMed PMID: 25117291.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Protons modulate perivascular axo-axonal neurotransmission in the rat mesenteric artery. AU - Takatori,Shingo, AU - Hirai,Kazuhiro, AU - Ozaki,Shuichiro, AU - Tangsucharit,Panot, AU - Fukushima-Miyashita,Satoko, AU - Goda,Mitsuhiro, AU - Hashikawa-Hobara,Narumi, AU - Ono,Nobufumi, AU - Kawasaki,Hiromu, PY - 2013/10/07/received PY - 2014/07/07/revised PY - 2014/08/01/accepted PY - 2014/8/14/entrez PY - 2014/8/15/pubmed PY - 2015/7/29/medline SP - 5743 EP - 56 JF - British journal of pharmacology JO - Br J Pharmacol VL - 171 IS - 24 N2 - BACKGROUND AND PURPOSE: Previous 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 APPROACH: Perfusion 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 RESULTS: Periarterial 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 Ca(2+) -free medium. CONCLUSION AND IMPLICATION: These results suggest that protons are released from perivascular adrenergic and CGRPergic nerves upon PNS and these protons modulate transmission in CGRPergic nerves. SN - 1476-5381 UR - https://www.unboundmedicine.com/medline/citation/25117291/Protons_modulate_perivascular_axo_axonal_neurotransmission_in_the_rat_mesenteric_artery_ L2 - https://doi.org/10.1111/bph.12878 DB - PRIME DP - Unbound Medicine ER -