title: Capsaicin modulates acetylcholine release at the myoneural junction.
abstract: Transient receptor potential (TRP) proteins are non-selective cation channel proteins that are expressed throughout the body. Previous studies demonstrated the expression of TRP Vanilloid 1 (TRPV1), capsaicin (CAP) receptor, in sensory neurons. Recently, we reported TRPV1 expression in mouse motor nerve terminals [MNTs; (Thyagarajan et al., 2009)], where we observed that CAP protected MNTs from botulinum neurotoxin A (BoNT/A). Phrenic nerve diaphragm nerve muscle preparations (NMP) isolated from isoflurane anesthetized adult mice were analyzed for twitch tension, spontaneous (mEPCs) and nerve stimulus evoked (EPCs) acetylcholine release. When acutely applied to isolated NMP, CAP produced a concentration-dependent decline of twitch tension and produced a significant decline in the amplitude of EPCs and quantal content without any effect on the mEPCs. The suppression of nerve stimulus evoked acetylcholine release by CAP was antagonized by capsazepine (CPZ), a TRPV1 antagonist. CAP did not suppress phrenic nerve stimulus evoked acetylcholine release in TRPV1 knockout mice. Also, CAP treatment, in vitro, interfered with the localization of adapter protein 2 in cholinergic Neuro 2a cells. Wortmannin, (WMN; non-selective phosphoinositol kinase inhibitor), mimicked the effects of CAP by inhibiting the acetylcholine exocytosis. Our data suggest that TRPV1 proteins expressed at the MNT are coupled to the exo-endocytic mechanisms to regulate neuromuscular functions.
authors.affiliation: School of Pharmacy, University of Wyoming, WY 82071, USA. Electronic address: bthyagar@uwyo.edu.
authors.forename: Baskaran
authors.initials: B
authors.lastname: Thyagarajan
authors.affiliation: Department of Pharmacology and Physiology, Rutgers University - New Jersey Medical School, Newark, NJ 07103, USA.
authors.forename: Joseph G
authors.initials: JG
authors.lastname: Potian
authors.affiliation: School of Pharmacy, University of Wyoming, WY 82071, USA.
authors.forename: Padmamalini
authors.initials: P
authors.lastname: Baskaran
authors.affiliation: Department of Pharmacology and Physiology, Rutgers University - New Jersey Medical School, Newark, NJ 07103, USA.
authors.forename: Joseph J
authors.initials: JJ
authors.lastname: McArdle
mesh_terms: D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D002211:Capsaicin / Q000031:analogs & derivatives / Q000494:pharmacology*; D005089:Exocytosis / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D009469:Neuromuscular Junction / Q000187:drug effects* / Q000378:metabolism*; D010791:Phrenic Nerve / Q000187:drug effects / Q000378:metabolism; D050916:TRPV Cation Channels / Q000378:metabolism; D055536:Vagus Nerve Stimulation / Q000379:methods
chemical_list: D050916:TRPV Cation Channels; C493921:TRPV1 protein, mouse; C071423:capsazepine; D000109:Acetylcholine; D002211:Capsaicin
keywords: Acetylcholine release; Capsaicin; Capsaicin (PubChem CID: 1548943); Endocytosis; Exocytosis; Motor nerve terminal; Phosphatidylinositol-4,5-bisphosphate (PubChem CID: 5311358GTPL2387); TRPV1; capsazepine (PubChem CID: 2733484