title: Nicotine facilitates reinnervation of phenol-injured perivascular adrenergic nerves in the rat mesenteric resistance artery.
abstract: Nicotine has been shown to have neuroprotective and neurotrophic actions in the central nervous system. To elucidate the peripheral neurotrophic effects of nicotine, we determined whether nicotine affected the reinnervation of mesenteric perivascular nerves following a topical phenol treatment. A topical phenol treatment was applied to the superior mesenteric artery proximal to the abdominal aorta in Wistar rats. We examined the immunohistochemistry of the distal small arteries 7 days after the treatment. The topical phenol treatment markedly reduced the density of tyrosine hydroxylase (TH)-LI and calcitonin gene-related peptide (CGRP)-LI fibers in these arteries. The administration of nicotine at a dose of 3 mg/kg/day (1.5 mg/kg/injection, twice a day), but not once a day or its continuous infusion using a mini-pump significantly increased the density of TH-LI nerves without affecting CGRP-LI nerves. A pretreatment with nicotinic acetylcholine receptor antagonists hexamethonium, mecamylamine, and methyllycaconitine, but not dextrometorphan, canceled the TH-LI nerve reinnervation induced by nicotine. Nicotine significantly increased NGF levels in the superior cervical ganglia (SCG) and mesenteric arteries, but not in the dorsal root ganglia, and also up-regulated the expression of NGF receptors (TrkA) in the SCG, which were canceled by hexamethonium. These results suggested that nicotine exhibited neurotrophic effects that facilitated the reinnervation of adrenergic TH-LI nerves by activating α7 nicotinic acetylcholine receptor and NGF in the SCG.
authors.affiliation: Department of Clinical Pharmacy, College of Pharmaceutical Sciences, Matsuyama University, 4-2 Bunkyo-cho, Matsuyama, Ehime 790-8578, Japan; Department of Clinical Pharmaceutical Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, 1-1-1 Tsushima-naka, Kita-ku, Okayama 700-8530, Japan. Electronic address: stakator@cc.matsuyama-u.ac.jp.
authors.forename: Shingo
authors.initials: S
authors.lastname: Takatori
authors.affiliation: Department of Clinical Pharmaceutical Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, 1-1-1 Tsushima-naka, Kita-ku, Okayama 700-8530, Japan.
authors.forename: Hidetoshi
authors.initials: H
authors.lastname: Fujiwara
authors.affiliation: Department of Clinical Pharmaceutical Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, 1-1-1 Tsushima-naka, Kita-ku, Okayama 700-8530, Japan.
authors.forename: Kenta
authors.initials: K
authors.lastname: Hagimori
authors.affiliation: Department of Life Science, Okayama University of Science, 1-1 Ridai-cho, Kita-ku, Okayama 700-0005, Japan.
authors.forename: Narumi
authors.initials: N
authors.lastname: Hashikawa-Hobara
authors.affiliation: Department of Clinical Pharmaceutical Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, 1-1-1 Tsushima-naka, Kita-ku, Okayama 700-8530, Japan.
authors.forename: Ayako
authors.initials: A
authors.lastname: Yokomizo
authors.affiliation: Department of Clinical Pharmaceutical Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, 1-1-1 Tsushima-naka, Kita-ku, Okayama 700-8530, Japan.
authors.forename: Fusako
authors.initials: F
authors.lastname: Takayama
authors.affiliation: Department of Clinical Pharmaceutical Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, 1-1-1 Tsushima-naka, Kita-ku, Okayama 700-8530, Japan.
authors.forename: Panot
authors.initials: P
authors.lastname: Tangsucharit
authors.affiliation: Department of Drug Information, Faculty of Pharmaceutical Sciences, Fukuoka University, 1-1-1 Nanakuma, 818-8530 Fukuoka, Japan.
authors.forename: Nobufumi
authors.initials: N
authors.lastname: Ono
authors.affiliation: Department of Clinical Pharmacy, College of Pharmaceutical Sciences, Matsuyama University, 4-2 Bunkyo-cho, Matsuyama, Ehime 790-8578, Japan; Department of Clinical Pharmaceutical Science, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, 1-1-1 Tsushima-naka, Kita-ku, Okayama 700-8530, Japan; Department of Drug Information, Faculty of Pharmaceutical Sciences, Fukuoka University, 1-1-1 Nanakuma, 818-8530 Fukuoka, Japan.
authors.forename: Hiromu
authors.initials: H
authors.lastname: Kawasaki
mesh_terms: D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism; D005727:Ganglia, Spinal / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D005786:Gene Expression Regulation / Q000187:drug effects; D008638:Mesenteric Arteries / Q000294:innervation*; D009412:Nerve Fibers / Q000187:drug effects* / Q000502:physiology*; D009414:Nerve Growth Factors / Q000378:metabolism; D009416:Nerve Regeneration / Q000187:drug effects*; D009538:Nicotine / Q000494:pharmacology*; D019800:Phenol / Q000009:adverse effects*; D051381:Rats; D017208:Rats, Wistar; D020917:Receptor, trkA / Q000378:metabolism; D011978:Receptors, Nicotinic / Q000378:metabolism; D017783:Superior Cervical Ganglion / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
chemical_list: D009414:Nerve Growth Factors; D011978:Receptors, Nicotinic; D019800:Phenol; D009538:Nicotine; D014446:Tyrosine 3-Monooxygenase; D020917:Receptor, trkA; D015740:Calcitonin Gene-Related Peptide
keywords: Dextrometorphan hydrobromide (PubChem CID: 5464025); Hexamethonium bromide (PubChem CID: 5938); Mecamylamine hydrochloride (PubChem CID: 13221); Methyllycaconitine citrate (PubChem CID: 16219626); Nerve growth factor; Nicotine; Nicotine hydrogen tartrate salt (PubChem CID: 11957628); Rat mesenteric artery; Tyrosine hydroxylase-containing adrenergic nerves; α7 Nicotinic acetylcholine receptor