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Endogenous cannabinoid, anandamide, acts as a noncompetitive inhibitor on 5‐HT 3 receptor‐mediated responses in Xenopus oocytes
Author(s) -
Oz Murat,
Zhang Li,
Morales Marisela
Publication year - 2002
Publication title -
synapse
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.809
H-Index - 106
eISSN - 1098-2396
pISSN - 0887-4476
DOI - 10.1002/syn.10121
Subject(s) - anandamide , cannabinoid receptor , cannabinoid , endocannabinoid system , chemistry , depolarization induced suppression of inhibition , receptor , xenopus , gpr18 , antagonist , pharmacology , cannabinoid receptor antagonist , endocrinology , medicine , biology , biochemistry , gene
The cloned 5‐HT 3 receptor from NCB‐20 neuroblastoma cells was expressed in Xenopus oocytes and the effect of the endogenous cannabinoid ligand, anandamide, was investigated on the function of this receptor. The oocytes expressing the cloned 5‐HT 3 receptors were voltage‐clamped at −70 mV. Anandamide, at the concentration range of 0.1–100 μM, reversibly inhibited 1 μM 5‐HT induced currents. The inhibition of 5‐HT induced currents by anandamide was concentration‐dependent with an EC 50 of 3.7 μM and slope value of 0.94. This inhibitory effect was not dependent on the membrane potential and anandamide did not have an effect on the reversal potential of 5‐HT‐induced currents. In the presence of 10 μM anandamide, the maximum 5‐HT‐induced response was also inhibited and the respective EC 50 values were 3.4 μM and 3.1 μM in the absence and presence of anandamide, indicating that anandamide acts as a noncompetitive antagonist on 5‐HT 3 receptors. CB 1 receptor antagonist SR‐141716A (1 μM) and pertussis toxin (5 μg/ml) did not cause a significant change on the inhibition of 5‐HT responses by anandamide. The effect of anandamide was not changed by preincubating the oocytes with 0.2 mM 8‐Br‐cAMP, a membrane‐permeable analog of cAMP, or Sp‐cAMPS (0.1 mM), a membrane‐permeable protein kinase A activator. These results suggest that the effect of anandamide is independent of the activation of cAMP pathway and not mediated by the activation of PTX sensitive G‐proteins. In conclusion, we demonstrated that the endogenous cannabinioid anandamide inhibits the function of 5‐HT 3 receptors expressed in Xenopus oocytes in a cannabinoid‐receptor independent and noncompetitive manner. Synapse 46:150–156, 2002. Published 2002 Wiley‐Liss, Inc.