Cultured chick sympathetic neurons: modulation of electrically evoked noradrenaline release by P2-purinoceptors.
The present study investigates the pharmacological profile of P2-purinoceptors modulating noradrenaline release from cultured chick sympathetic neurons. ATP (30 microM-3 mM) and 2-methylthio-ATP (3-100 microM), but not alpha, beta-methylene-ATP (up to 100 microM), caused a significant facilitation of electrically evoked [3H]-noradrenaline release when added 2 min before depolarization. The facilitation declined with time of exposure suggesting receptor desensitization. The facilitatory effect was markedly diminished by the P2-purinoceptor antagonists reactive blue 2 (3 microM) and suramin (300 microM), but not changed by mecamylamine (10 microM), a nicotinic receptor antagonist. At 1 mM and higher concentrations, ATP added for 12 min, inhibited noradrenaline release; release was virtually abolished by 6 mM ATP. The inhibitory effect of ATP was slightly diminished by suramin but not affected by reactive blue 2. Electrically evoked [3H]-noradrenaline release remained unaffected in the presence of the adenosine (P1)-receptor agonists R(-)N6-(2-phenylisopropyl)adenosine (R-PIA), 2-[p-(2-carboxyethyl) phenylethylamino]-5'-N-ethylcarboxamidoadenosine (NECA), and N6-2-(4-aminophenyl)ethyladenosine (APNEA), used up to 1 microM. The present results confirm the existence of two P2-purinoceptors affecting noradrenaline release: 1) a facilitatory receptor which is activated by 2-methylthio-ATP as well as ATP, and blocked by suramin as well as reactive blue 2, and 2) an inhibitory receptor which is activated by ATP, only slightly affected by suramin but not at all by reactive blue 2 and does not belong to the established P2-purinoceptor subtypes.
D000255:Adenosine Triphosphate / Q000031:analogs & derivatives* / Q000494:pharmacology*; D000320:Adrenergic Fibers / Q000502:physiology*; D000818:Animals; D002478:Cells, Cultured; D002642:Chick Embryo; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D009638:Norepinephrine / Q000378:metabolism*; D011983:Receptors, Purinergic / Q000187:drug effects*; D013498:Suramin / Q000494:pharmacology; D013997:Time Factors
D011983:Receptors, Purinergic; D013498:Suramin; D000255:Adenosine Triphosphate; D009638:Norepinephrine