{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,5]],"date-time":"2026-04-05T01:48:46Z","timestamp":1775353726877,"version":"3.50.1"},"reference-count":36,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2002,9,3]],"date-time":"2002-09-03T00:00:00Z","timestamp":1031011200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Synapse"],"published-print":{"date-parts":[[2002,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The cloned 5\u2010HT<jats:sub>3<\/jats:sub> receptor from NCB\u201020 neuroblastoma cells was expressed in <jats:italic>Xenopus<\/jats:italic> oocytes and the effect of the endogenous cannabinoid ligand, anandamide, was investigated on the function of this receptor. The oocytes expressing the cloned 5\u2010HT<jats:sub>3<\/jats:sub> receptors were voltage\u2010clamped at \u221270 mV. Anandamide, at the concentration range of 0.1\u2013100 \u03bcM, reversibly inhibited 1 \u03bcM 5\u2010HT induced currents. The inhibition of 5\u2010HT induced currents by anandamide was concentration\u2010dependent with an EC<jats:sub>50<\/jats:sub> of 3.7 \u03bcM 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\u2010HT\u2010induced currents. In the presence of 10 \u03bcM anandamide, the maximum 5\u2010HT\u2010induced response was also inhibited and the respective EC<jats:sub>50<\/jats:sub> values were 3.4 \u03bcM and 3.1 \u03bcM in the absence and presence of anandamide, indicating that anandamide acts as a noncompetitive antagonist on 5\u2010HT<jats:sub>3<\/jats:sub> receptors. CB<jats:sub>1<\/jats:sub> receptor antagonist SR\u2010141716A (1 \u03bcM) and pertussis toxin (5 \u03bcg\/ml) did not cause a significant change on the inhibition of 5\u2010HT responses by anandamide. The effect of anandamide was not changed by preincubating the oocytes with 0.2 mM 8\u2010Br\u2010cAMP, a membrane\u2010permeable analog of cAMP, or Sp\u2010cAMPS (0.1 mM), a membrane\u2010permeable 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\u2010proteins. In conclusion, we demonstrated that the endogenous cannabinioid anandamide inhibits the function of 5\u2010HT<jats:sub>3<\/jats:sub> receptors expressed in <jats:italic>Xenopus<\/jats:italic> oocytes in a cannabinoid\u2010receptor independent and noncompetitive manner. Synapse 46:150\u2013156, 2002. 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