title: Adenosine inhibits voltage-dependent Ca2+ currents in rat dissociated supraoptic neurones via A1 receptors.
abstract: 1. The modulation of voltage-dependent Ca2+ currents (ICa) by adenosine was investigated in magnocellular neurones acutely dissociated from the rat hypothalamic supraoptic nucleus (SON) by using the whole-cell patch-clamp technique. 2. Adenosine dose dependently and reversibly inhibited ICa elicited by depolarizing voltage steps from a holding potential of -80 mV to potentials ranging from -30 to +20 mV. The mean (+/- s.e.m.) maximum inhibition rate was 36.1 +/- 4.1 % (n = 6) at -20 mV and the EC50 was 9.8 x 10-7 M (n = 6). 3. The inhibition of ICa by adenosine was completely reversed by the selective A1 receptor antagonist 8-cyclopentyl theophylline (CPT), and was mimicked by the selective A1 receptor agonist N 6-cyclohexyladenosine (CHA). 4. The inhibition by CHA was strongly reduced when ICa was inhibited by omega-conotoxin GVIA, a blocker of N-type Ca2+ channels. 5. The adenosine-induced inhibition of ICa was largely reversed by a depolarizing prepulse to +150 mV for 100 ms, which is known to reverse the inhibition of Ca2+ channels mediated by G-protein betagamma subunits. 6. The adenosine receptor-mediated inhibition of ICa was not abolished by intracellularly applied preactivated pertussis toxin (PTX). 7. Using immunohistochemistry, Gzalpha-like immunoreactivity (a PTX-resistant inhibitory G-protein) was observed throughout the SON. 8. These results suggest that adenosine modulates the neuronal activity of SON neurones by inhibiting N-type voltage-dependent Ca2+ channels via A1 receptors which are coupled to PTX-resistant G-proteins.
authors.affiliation: Department of Physiology, School of Medicine, University of Occupational and Environmental Health, Kitakyushu 807-8555, Japan. n-jun@med.uoeh-u.ac.jp
authors.forename: J
authors.initials: J
authors.lastname: Noguchi
authors.forename: H
authors.initials: H
authors.lastname: Yamashita
mesh_terms: D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D000818:Animals; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology*; D020864:Calcium Channels, N-Type / Q000187:drug effects / Q000502:physiology; D066298:In Vitro Techniques; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D018408:Patch-Clamp Techniques; D051381:Rats; D017208:Rats, Wistar; D043705:Receptor, Adenosine A2A; D043704:Receptor, Adenosine A2B; D043684:Receptor, Adenosine A3; D018047:Receptors, Purinergic P1 / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013495:Supraoptic Nucleus / Q000502:physiology*; D013779:Tetrodotoxin / Q000494:pharmacology; D013805:Theobromine / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: D015220:Calcium Channels; D020864:Calcium Channels, N-Type; D043705:Receptor, Adenosine A2A; D043704:Receptor, Adenosine A2B; D043684:Receptor, Adenosine A3; D018047:Receptors, Purinergic P1; C056426:CGS 24012; C027513:N(6)-cyclohexyladenosine; D013779:Tetrodotoxin; C057837:3,7-dimethyl-1-propargylxanthine; D000241:Adenosine; D013805:Theobromine