title: TRPV1 gene deficiency attenuates miniature EPSC potentiation induced by mannitol and angiotensin II in supraoptic magnocellular neurons.
abstract: The release of arginine vasopressin (AVP) from the magnocellular neurosecretory cells (MNCs) in the supraoptic nucleus (SON) is crucial for body fluid homeostasis. The MNC activity is modulated by synaptic inputs and humoral factors. A recent study demonstrated that an N-terminal splice variant of the transient receptor potential vanilloid type 1 (TRPV1) is essential for osmosensory transduction in the SON. In the present study, we examined the effects of mannitol and angiotensin II on miniature EPSCs (mEPSCs) in the supraoptic MNCs using whole-cell patch-clamp recording in in vitro slice preparation. Mannitol (60 mm) and angiotensin II (0.1 microm) increased the frequency of mEPSCs without affecting the amplitude. These effects were attenuated by pre-exposure to a nonspecific TRPV channel blocker, ruthenium red (10 microm) and enhanced by pre-exposure to cannabinoid type1 receptor antagonist, AM251 (2 microm). Mannitol-induced potentiation of mEPSCs was not attenuated by angiotensin II receptor antagonist, losartan (10 microm), indicating independent pathways of mannitol and angiotensin II to the TRPV channels. The potentiation of mEPSCs by mannitol was not mimicked by a TRPV1 agonist, capsaicin, and also not attenuated by TRPV1 blockers, capsazepine (10 microm). PKC was involved in angiotensin II-induced potentiation of mEPSCs. The effects of mannitol and angiotensin II on the supraoptic MNCs in trpv1 knock-out mice were significantly attenuated compared with those in wild-type mice counterparts. The results suggest that hyperosmotic stimulation and angiotensin II independently modulate mEPSCs through capsaicin-insensitive TRPV1 channel in the presynaptic terminals of the SON.
authors.affiliation: Department of Physiology, School of Medicine, University of Occupational and Environmental Health, Kitakyushu 807-8555, Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Yokoyama
authors.forename: Takeshi
authors.initials: T
authors.lastname: Saito
authors.forename: Toyoaki
authors.initials: T
authors.lastname: Ohbuchi
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Hashimoto
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Suzuki
authors.forename: Hiroki
authors.initials: H
authors.lastname: Otsubo
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Fujihara
authors.forename: Toshihisa
authors.initials: T
authors.lastname: Nagatomo
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Ueta
mesh_terms: D000704:Analysis of Variance; D000804:Angiotensin II / Q000494:pharmacology*; D000813:Anilides / Q000494:pharmacology; D000818:Animals; D002211:Capsaicin / Q000031:analogs & derivatives / Q000494:pharmacology; D002614:Chelating Agents / Q000494:pharmacology; D002934:Cinnamates / Q000494:pharmacology; D004234:Diuretics, Osmotic / Q000494:pharmacology*; D004347:Drug Interactions; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D008353:Mannitol / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D055369:Miniature Postsynaptic Potentials / Q000187:drug effects* / Q000235:genetics*; D009474:Neurons / Q000187:drug effects*; D010880:Piperidines / Q000494:pharmacology; D011719:Pyrazines / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects; D013495:Supraoptic Nucleus / Q000166:cytology*; D050916:TRPV Cation Channels / Q000172:deficiency*; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
chemical_list: D000813:Anilides; D002614:Chelating Agents; D002934:Cinnamates; D004234:Diuretics, Osmotic; D004791:Enzyme Inhibitors; C477659:N-(3-methoxyphenyl)-4-chlorocinnamanilide; C475772:N-(4-tert-butylphenyl)-4-(3-chloropyridin-2-yl)tetrahydropyrazine-1(2H)-carboxamide; D010880:Piperidines; D011719:Pyrazines; D011720:Pyrazoles; D011725:Pyridines; D050916:TRPV Cation Channels; C493921:TRPV1 protein, mouse; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; C103505:AM 251; D008353:Mannitol; D004533:Egtazic Acid; C025603:1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid; C071423:capsazepine; D002211:Capsaicin