Effects of cannabinoids on endogenous K+ and Ca2+ currents in HEK293 cells.
Effects of cannabinoids on endogenous potassium and calcium currents in HEK293 cells were studied using the whole-cell variant of the patch-clamp technique. The cannabinoid agonists WIN 55,212-2, methanandamide, and anandamide (1 microM) decreased the calcium current by 53.1 +/- 2.6, 47.5 +/- 1.2, and 38.8 +/- 3.1%, respectively, after transfection of human CB1 cannabinoid receptor (hCB1) cDNA into HEK293 cells. The delayed rectifier-like current was not changed after application of these agonists, but the inward rectifier was increased by 94.0 +/- 3.6, 83.7 +/- 5.1, and 63.0 +/- 2.5% after application of WIN 55,212-2, methanandamide, and anandamide, respectively. The effects of the cannabinoid antagonists (AM251, AM281, and AM630) on the inward rectifier and calcium currents were the opposite of those seen with cannabinoid agonists; thus, these compounds act as inverse agonists in this preparation. These results suggest that endogenous inward rectifier and calcium currents are modulated by cannabinoids in HEK293 cells, and that some expressed receptors may be constitutively active.
Vásquez
Clemente
C
Centro Universitario de Investigaciones Biomédicas, Universidad de Colima, Avenida 25 de julio # 965, Colonia Villa de San Sebastián, Colima, Colima, CP 28040, México. clemvas@cgic.ucol.mx
Navarro-Polanco
Ricardo A
RA
Huerta
Miguel
M
Trujillo
Xóchitl
X
Andrade
Felipa
F
Trujillo-Hernández
Benjamín
B
Hernández
Leonardo
L
D001095:Arachidonic Acids / Q000494:pharmacology; D048588:Benzoxazines; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology*; D002186:Cannabinoids / Q000378:metabolism* / Q000494:pharmacology; D002460:Cell Line; D063388:Endocannabinoids; D006801:Humans; D008564:Membrane Potentials / Q000187:drug effects; D009025:Morpholines / Q000494:pharmacology; D009281:Naphthalenes / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D053284:Polyunsaturated Alkamides; D011188:Potassium / Q000378:metabolism; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology*; D043884:Receptor, Cannabinoid, CB1 / Q000819:agonists
D001095:Arachidonic Acids; D048588:Benzoxazines; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D002186:Cannabinoids; D063388:Endocannabinoids; D009025:Morpholines; D009281:Naphthalenes; D053284:Polyunsaturated Alkamides; D015221:Potassium Channels; D043884:Receptor, Cannabinoid, CB1; C088155:methanandamide; C070417:(3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone; D011188:Potassium; D002118:Calcium; C078814:anandamide