Reference

Cannabinoid receptor-mediated inhibition of dopamine release in the retina

Cannabinoid receptor-mediated inhibition of dopamine release in the retina. Schlicker, Eberhard; Timm, Joerg; Goethert, Manfred (Institut Pharmakologie Toxikologie, Rheinische Friedrich-Wilhelms-Universitaet, Bonn D-53113, Germany). Naunyn-Schmiedeberg's Archives of Pharmacology, 354(6), 791-795 (English) 1996 Springer. CODEN: NSAPCC. ISSN: 0028-1298. DOCUMENT TYPE: Journal CA Section: 1 (Pharmacology) Section cross-reference(s): 2 The possible occurrence of cannabinoid (CB) receptors was studied on superfused guinea-pig retinal disks preincubated with [3H]dopamine ([3H]DA) or [3H]noradrenaline ([3H]NA). Tritium overflow was evoked either elec. (3 Hz) or by re-introduction of Ca2+ 1.3 mM after superfusion with Ca2+-free medium contg.Some commonly used reagents like 51-61-6 and 83002-04-4 are used in this experiment. K+ 30 mM. The accumulation of [3H]DA and [3H]NA was inhibited by the selective inhibitor of the neuronal dopamine transporter GBR-12909 (pIC50% 7.29 and 7.41, resp.) but not by the selective inhibitor of the neuronal noradrenaline transporter desipramine (1 mM). The elec. or Ca2+-evoked tritium overflow in retinal disks preincubated with [3H]DA or [3H]NA was reduced by the CB receptor agonists P-55,940 and WIN 55,2122 (pIC50% in disks preincubated with [3H]NA, elec. stimulation: 7.03 and 6.70, resp.) but not affected by the inactive S(-)enantiomer of the latter, WIN 55,2123 (up to 10 mM). The concn.-response curve of WIN 55,2122 was shifted to the right by the CB1 receptor antagonist SR 141716 (apparent pA2: 8.29) which, by itself, increased the evoked overflow. The facilitatory effect of SR 141716 was not affected by GBR-12909 and the dopamine receptor antagonist haloperidol. In conclusion, the dopaminergic neurons of the guinea-pig retina can be labeled by both [3H]DA and [3H]NA. Transmitter release from the dopaminergic neurons is inhibited by activation of cannabinoid receptors of the CR1 type, which appear to be tonically activated by an endogenous CB receptor ligand. .

Characterization of CB1 receptors on rat neuronal cell cultures: binding and functional studies using the selective receptor antagonist SR 141716A

Characterization of CB1 receptors on rat neuronal cell cultures: binding and functional studies using the selective receptor antagonist SR 141716A. Jung, M.; Calassi, R.; Rinaldi-Carmona, M.; Chardenot, P.; Le Fur, G.; Soubrie, P.; Oury-Donat, F.Chemicals with cas numbers 83002-04-4 and 60-92-4 also play role. (Sanofi Recherche, Montpellier, Fr.). Journal of Neurochemistry, 68(1), 402-409 (English) 1997 Lippincott-Raven. CODEN: JONRA9. ISSN: 0022-3042. DOCUMENT TYPE: Journal CA Section: 1 (Pharmacology) Section cross-reference(s): 13 This study was undertaken to characterize further the central cannabinoid receptors in rat primary neuronal cell cultures from selected brain structures. By using [3H]SR 141716A, the specific CB1 receptor antagonist, the authors demonstrate in cortical neurons the presence of a high d. of specific binding sites (Bmax = 139 fmol/mg of protein) displaying a high affinity (KD = 0.76 nM). The two cannabinoid receptor agonists, CP 55940 and WIN 55212-2, inhibited in a concn.-dependent manner cAMP prodn. induced by either 1 mM forskolin or isoproterenol with EC50 values in the nanomolar range (4.6 and 65 nM with forskolin and 1.0 and 5.1 nM with isoproterenol for CP 55940 and WIN 55212-2, resp.). Moreover, in striatal neurons and cerebellar granule cells, CP 55940 was also able to reduce the cAMP accumulation induced by 1 mM forskolin with a potency similar to that obsd. in cortical neurons (EC50 values of 3.5 and 1.9 nM in striatum and cerebellum, resp.). SR 141716A antagonized the CP 55940- and WIN 55212-2-induced inhibition of cAMP accumulation, suggesting CB1 receptor-specific mediation of these effects on all primary cultures tested. Furthermore, CP 55940 was unable to induce mitogen-activated protein kinase activation in either cortical or striatal neurons. In conclusion, the results show nanomolar efficiencies for CP 55940 and WIN 55212-2 on adenylyl cyclase activity and no effect on any other signal transduction pathway investigated in primary neuronal cultures. .