title: Dual modulation of calcium channel current via recombinant alpha2-adrenoceptors in pheochromocytoma (PC-12) cells.
abstract: The ability of recombinant rat alpha2D-and alpha2B-adrenoceptors expressed in nerve-growth-factor-differentiated pheochromocytoma PC-12 cells to modulate Ca2+ currents, recorded by the whole-cell patch-clamp technique, has been studied. Ca2+ currents in different cells were either reversibly reduced or increased by dexmedetomidine, an alpha2-adrenergic agonist, in a concentration-dependent manner. Pertussis toxin pretreatment reduced the number of cells that showed an inhibitory response and reduced the magnitude of inhibition. In cells expressing the alpha2B-adrenoceptor, pertussis toxin increased the proportion of cells from which a stimulatory effect on Ca2+ currents could be recorded. The magnitude of the inhibitory responses was unaffected but the stimulatory responses were considerably reduced by the dihydropyridine Ca2+ channel blocker nifedipine (5 microM). All effects of dexmedetomidine were reversible upon wash-out and inhibited by the antagonist rauwolscine. The results support the idea that modulation of voltage-dependent Ca2+ channels in transfected PC-12 cells is mediated by activation of recombinant alpha2D- and alpha2B-adrenoceptors. This receptor activation predominantly causes inhibition of dihydropyridine-insensitive Ca2+ channels via pertussis-toxin-sensitive G proteins. Additionally receptor activation can also lead to stimulation of dihydropyridine-sensitive Ca2+ channels via pertussis-toxin-insensitive mechanisms.
authors.affiliation: Centre for Biotechnology, University of Turku and Abo Akademi University, PO Box 123, FIN-20521 Turku, Finland.
authors.forename: S L
authors.initials: SL
authors.lastname: Soini
authors.forename: E
authors.initials: E
authors.lastname: Duzic
authors.forename: S M
authors.initials: SM
authors.lastname: Lanier
authors.forename: K E
authors.initials: KE
authors.lastname: Akerman
mesh_terms: D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology*; D000242:Cyclic AMP / Q000494:pharmacology; D004553:Electric Conductivity; D019204:GTP-Binding Proteins / Q000502:physiology; D007093:Imidazoles / Q000494:pharmacology; D020926:Medetomidine; D009474:Neurons / Q000502:physiology*; D009543:Nifedipine / Q000494:pharmacology; D016716:PC12 Cells; D018408:Patch-Clamp Techniques; D037342:Pertussis Toxin; D051381:Rats; D011942:Receptors, Adrenergic, alpha / Q000502:physiology*; D011994:Recombinant Proteins; D014162:Transfection; D010566:Virulence Factors, Bordetella / Q000494:pharmacology; D015016:Yohimbine / Q000494:pharmacology
chemical_list: D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D007093:Imidazoles; D011942:Receptors, Adrenergic, alpha; D011994:Recombinant Proteins; D010566:Virulence Factors, Bordetella; D015124:8-Bromo Cyclic Adenosine Monophosphate; D015016:Yohimbine; D000242:Cyclic AMP; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins; D009543:Nifedipine; D020926:Medetomidine