CULTURED CHICK SYMPATHETIC NEURONS - MODULATION OF ELECTRICALLY-EVOKED NORADRENALINE RELEASE BY P-2-PURINOCEPTORS

The present study investigates the pharmacological profile of P-2-puri noceptors modulating noradrenaline release from cultured chick sympath etic neurons. ATP (30 mu M-3 mM) and 2-methylthio-ATP (3-100 mu M), bu t not alpha,beta-methylene-ATP (up to 100 mu M), caused a significant facilitation of electrically evoked [H-3]-noradrenaline release when a dded 2 min before depolarization. The facilitation declined with time of exposure suggesting receptor desensitization. The facilitatory effe ct was markedly diminished by the P-2-purinoceptor antagonists reactiv e blue 2 (3 mu M) and suramin (300 mu M), but not changed by mecamylam ine (10 mu M), a nicotinic receptor antagonist. At 1 mM and higher con centrations, ATP added for 12 min, inhibited noradrenaline release; re lease was virtually abolished by 6 mM ATP. The inhibitory effect of AT P was slightly diminished by suramin but not affected by reactive blue 2. Electrically evoked [H-3]-noradrenaline release remained unaffecte d in the presence of the adenosine (P-1)-receptor agonists R(-)N-6-(2- phenylisopropyl)adenosine (R-PIA), l)phenylethylamino]-5'-N-ethylcarbo xamidoadenosine (CGS-21680), 5'-N-ethylcarboxamidoadenosine (NECA), an d N-6-2-(4-aminophenyl)ethyladenosine (APNEA), used up to 1 mu M. The present results confirm the existence of two P-2-purinoceptors affecti ng noradrenaline release: 1) a facilitatory receptor which is activate d by 2-methylthio-ATP as well as ATP, and blocked by suramin as well a s reactive blue 2, and 2) an inhibitory receptor which is activated by ATP, only slightly affected by suramin but not at all by reactive blu e 2 and does not belong to the established P-2-purinoceptor subtypes.