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Cytochrome P-450 arachidonate metabolites affect the ion fluxes in rabbit medullary thick ascending limb (mTALH), which metabolizes arachidonite acid (AA) to various products. The AA metabolites do not proceed through potassium ion channels. The P-450-AA metabolites exhibit a furosemide-like effect as they primarily block the sodium ion, potassium ion and 2 chloride ion cotransporter of the mTALH cells.

Dopamine D3R are widely expressed in basal ganglia where interact with D1R. D3R potentiate cAMP accumulation and GABA release stimulated by D1R in striatonigral neurons through "atypical" signaling. During dopaminergic denervation, D3R signaling changes to a "typical" in which antagonizes the effects of D1R, the mechanisms of this switching are unknown. D3nf splice variant regulates membrane anchorage and function of D3R and decreases in denervation; thus, it is possible that D3R signaling switching correlates with changes in D3nf expression and increases of membranal D3R that mask D3R atypical effects. We performed experiments in unilaterally 6‐hydroxydopamine lesioned rats and found a decrease in mRNA and protein of D3nf, but not of D3R in the denervated striatum. Proximity ligation assay showed that D3R‐D3nf interaction decreased after denervation, whereas binding revealed an increased Bmax in D3R. The new D3R antagonized cAMP accumulation and GABA release stimulated by D1R; however, in the presence of N‐Ethylmaleimide (NEM), to block Gi protein signaling, activation of D3R produced its atypical signaling stimulating D1R effects. Finally, we investigated if the typical and atypical effects of D3R modulating GABA release are capable of influencing motor behavior. Injections of D3R agonist into denervated nigra decreased D1R agonist‐induced turning behavior but potentiated it in the presence of NEM. Our data indicate the coexistence of D3R typical and atypical signaling in striatonigral neurons during denervation that correlated with changes in the ratio of expression of D3nf and D3R isoforms. The coexistence of both atypical and typical signaling during denervation influences motor behavior. [ABSTRACT FROM AUTHOR]

Abstract: Recent studies suggested the expression of CB2 receptors in neurons of the CNS, however, most of these studies have only explored one aspect of the receptors, i.e., expression of protein, messenger RNA, or functional response, and more complete studies appear to be needed to establish adequately their role in the neuronal function. Electron microscopy studies showed the presence of CB2r in asymmetric terminals of the substantia nigra pars reticulata (SNr), and its mRNA appeared is expressed in the subthalamic nucleus. Here, we explore the expression, source, and functional effects of such receptors by different experimental approaches. Through PCR and immunochemistry, we showed mRNA and protein for CB2rs in slices and primary neuronal cultures from subthalamus. GW833972A, GW405833, and JHW 133, three CB2r agonists dose‐dependent inhibited K+‐induced [3H]‐Glutamate release in slices of SNr, and the two antagonist/inverse agonists, JTE‐907 and AM630, but not AM281, a CB1r antagonist, prevented GW833972A effect. Subthalamus lesions with kainic acid prevented GW833972A inhibition on release and decreased CB2r protein in nigral synaptosomes, thus nigral CB2rs originate in subthalamus. Inhibition of [3H]‐Glutamate release was PTX‐ and gallein‐sensitive, suggesting a Giβγ‐mediated effect. P/Q Ca2+‐type channel blocker, ω‐Agatoxin‐TK, also inhibited the [3H]‐Glutamate release, this effect was occluded with GW833972A inhibition, indicating that the βγ subunit effect is exerted on Ca2+channel activity. Finally, microinjections of GW833972A in SNr induced contralateral turning. Our data showed that presynaptic CB2rs inhibit [3H]‐Glutamate release in subthalamo‐nigral terminals by P/Q‐channels modulation through the Giβγ subunit and suggested their participation in motor behavior. [ABSTRACT FROM AUTHOR]