Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P21554 (cannabinoid receptor)
 3,582 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Presynaptic imidazoline receptors (IRs) which inhibit norepinephrine (NE) release from sympathetic nerve endings have been identified in cardiovascular tissue of man, rabbit, rat, and guinea pig. They do not belong to one of the classical presynaptic inhibitory receptor classes such as alpha 2-adrenoceptors or H3 histamine receptors, and there is also no relation to I1- and I2-imidazoline binding sites. Segments of human right atrial appendages preincubated with [3H]NE were used to determine unknown pharmacologic properties of the presynaptic IRs. In the presence of 1 microM rauwolscine, S23230, the (-)-enantiomer of the racemic oxazoline derivative S22687 (5-(2(methyl-phenoxy-methyl)-1,3-oxazoline-2-yl)amine) exhibited low potency in inhibiting the electrically evoked [3H]NE release (pIC30% = 4.96), whereas the (+)-enantiomer S23229 and the racemate S22687 were ineffective. The IR-mediated inhibitory effect of the imidazoline BDF 6143 (4-chloro-2-(2-imidazolin-2-ylamino)-isoindoline) and the guanidine aganodine on evoked [3H]NE release from sympathetic nerves in human atrial appendages was counteracted by rauwolscine (with very low potency) and by the cannabinoid CB1-receptor antagonist SR141715A (N-[piperdin-1-yl]-5-[4-chlorophenyl]-2,4-dichlorophenyl]-4- methyl-1H-pyrazole-3-carboxamide). The inhibitory effect of moxonidine on evoked [3H]NE release (which is exclusively mediated via activation of alpha 2-autoreceptors) was antagonized with high potency by rauwolscine, but not by SR141716A. The cannabinoid CB1 receptor agonists CP55,940([(-)-Cis-3-[2-hydroxy-4-(1,1-dimethylheptyl)phenyl] -trans-4- (3-hydroxy-propyl)cyclohexane]) and anandamide inhibited evoked [3H]NE release. Inhibition by CP55,940 and anandamide was abolished by 1 microM SR141716A as well as by 30 microM rauwolscine. In radioligand binding experiments on membranes from human atrial appendages (alpha 2- and sigma-binding sites were masked), cannabinoid receptor ligands and IR agonists displaced the radiolabeled guanidine derivative [3H]DTG (1,3-di-o-tolyguanidine, an agonist at presynaptic IRs) from its binding sites. Comparison of the potencies of these drugs determined in the competition experiments with [3H]DTG with those in inhibiting NE release via activation of the presynaptic IRs in the same tissue revealed a correlation. The present results suggest, e.g., that the presynaptic IRs may have certain binding domains in common with presynaptic cannabinoid receptors or that both receptors are different proteins which interact with each other in an unknown manner.
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PMID:Presynaptic imidazoline receptors. New developments in characterization and classification. 1041 12

The aim of the present study was to classify release-inhibiting receptors on rat pheochromocytoma PC12 cells. Veratridine-evoked [3H]noradrenaline release from PC12 cells was inhibited by micromolar concentrations of the imidazoline and guanidine derivatives cirazoline, clonidine, aganodine, 1,3-di(2-tolyl)guanidine, BDF6143 and agmatine, and of the cannabinoid receptor agonist WIN55,212-2 (R(+)-[2,3-dihydro-5-methyl-3-[(morpholinyl)methyl]pyrrolo-[1,2,3-de]-1,4-benzoxazin-yl](1-naphthalenyl)methanone mesylate), but not by noradrenaline. The inhibitory effect of clonidine was antagonized by micromolar concentrations of rauwolscine and SR141716A (N-[piperidin-1-yl]-5-[4-chlorophenyl]-1-[2,4-dichlorophenyl]-4-methyl-1H-pyrazole-3-carboxamide). The potencies of the agonists and antagonists were compatible with an action at previously characterized presynaptic imidazoline receptors. 1-Oleoyl-lysophosphatidic acid, but not sphingosine-1-phosphate, produced an inhibition of release that was antagonized by 30 microM rauwolscine, 1 microM SR141716A and 10 microM LY320135 as well as by pretreatment of the cells with 100 microM clonidine for 72 h. Polymerase chain reaction (PCR) experiments on cDNA from PC12 mRNA suggest mRNA expression of lysophospholipid receptors encoded by the genes edg2, edg3, edg5 and edg7, but not of receptors encoded by edg1, edg4, edg6 and edg8, and not of alpha(2A(-))nd CB(1) receptors. In conclusion, PC12 cells are not endowed with alpha(2)-adrenoceptors and CB(1) cannabinoid receptors, but with an inhibitory receptor recognizing imidazolines, guanidines and WIN55,212-2 similar to that on sympathetic nerves. The PCR results and the ability of 1-oleoyl-LPA to mimic these drugs (also with respect to their susceptibility to antagonists) suggest that the release-inhibiting receptor may be an edg-encoded lysophospholipid receptor.
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PMID:Noradrenaline release-inhibiting receptors on PC12 cells devoid of alpha(2(-)) and CB(1) receptors: similarities to presynaptic imidazoline and edg receptors. 1173 82