Cannabinoid receptor activation of G-proteins can be measured by WIN 55212-2-stimulated [35S]GTPgammaS binding. Receptor/transducer amplification factors, interpreted as the number of G-proteins activated per occupied receptor, are the ratio of the apparent B(max) of net agonist-stimulated [35S]GTPgammaS binding to the B(max) of receptor binding. The present study examined whether amplification...

The present study investigated the effect of the selective cannabinoid agonist, WIN 55212-2 [(4,5-dihydro-2-methyl-4(4-morpholinylmethyl)-1-(1-naphthalenyl-carbonyl)-6H-pyrrolo[3,2,1ij]quinolin-6-one], on body temperature. WIN 55212-2 (1, 2.5, 5, and 10 mg/kg, i.m.) induced hypothermia in a dose-dependent manner. The peak hypothermia occurred 60 to 180 min postinjection. Body temperature was st...

The relationship between GDP and cannabinoid-stimulated [35S]guanosine-5'-O-(3-thiotriphosphate) ([35S]GTPgammaS) binding was investigated in rat cerebellar membranes. Kinetic analyses showed that [35S]GTPgammaS binding reached steady-state levels and that the association rate was increased by the agonist WIN 55212-2 proportional to the concentration of GDP. Dissociation of [35S]GTPgammaS occur...

Chronic D-tetrahydrocannabinol (D-THC) administration produces tolerance to cannabinoid effects, but alterations in signal transduction that mediate these changes are not yet known. The present study uses in vitro autoradiography of agoniststimulated [S]GTPgS binding to localize cannabinoid receptor-activated G-proteins after chronic D-THC treatment. Cannabinoid (WIN 55212-2)-stimulated [S]GTPg...

CB(1) cannabinoid receptors mediate profound hypothermia when cannabinoid agonists are administered to rats. Glutamate, the principal excitatory neurotransmitter in the central nervous system (CNS), is thought to tonically increase body temperature by activating N-methyl-D-aspartate (NMDA) receptors. Because NMDA antagonists block cannabinoid-induced antinociception and catalepsy, intimate glut...

Cannabinoid CB1 receptor (via Gs) and dopamine D2 receptor (via Gi/o) antagonistically modulate goldfish cone membrane currents. As ON bipolar cells have CB1 and D1 receptors, but not D2 receptors, we focused on whether CB1 receptor agonist and dopamine interact to modulate voltage-dependent outward membrane K+ currents I K(V) of the ON mixed rod/cone (Mb) bipolar cells. Whole-cell currents wer...

When Mao died in 1976, Russia appeared better poised than China to become an important commerical and industrial power in the global economy. Yet it is China rather than Russia that has embraced globalization and developed trade and manufacturing, exporting increasingly higher-value-added goods. The explanation for this surprising outcome in found is Chinese elites viewing globalization as thei...

OBJECTIVE To evaluate the effects of WIN 55212-2, a cannabinoid receptor agonist, on intraocular pressure and aqueous humor dynamics in normal monkeys and monkeys with glaucoma. METHODS Intraocular pressure was measured prior to and up to 6 hours after the topical administration of WIN 55212-2 to 1 eye of 5 normal monkeys and to the glaucomatous eye of 8 monkeys with unilateral laser-induced ...

Cannabinoids protect neurons from excitotoxic injury. We investigated the mechanisms involved by studying N-methyl-D-aspartate (NMDA) toxicity in cultured murine cerebrocortical neurons in vitro and mouse cerebral cortex in vivo. The cannabinoid agonist R(+)-[2,3-dihydro-5-methyl-3-[(morpholinyl)-methyl]pyrrolo[1,2,3-de]-1,4-benzoxazin-yl]-(1-naphthalenyl)-methanone mesylate [R(+)-Win 55212] re...