Ca(2+)-dependent release from rat brain of cannabinoid receptor binding activity.

Abstract:

:As a result of the identification, pharmacological characterization, and localization of the cannabinoid receptor in the CNS, the existence of an endogenous ligand for this receptor can be hypothesized. Following the premise that such a substance could have the properties of a neuromodulator being stored in intracellular vesicles, we tested the ability of increased intracellular Ca2+ levels to stimulate release. We demonstrate here that the Ca2+ ionophore A23187 can induce release of cannabinoid-like binding activity in the presence but not in the absence of Ca2+. The effect of A23187 was maximal at 1.2 microM, consistent with vesicular release. It was necessary to increase the concentration of extracellular free Ca2+ to greater than 60 nM to evoke release. The released cannabinoid-like binding activity displaced [3H]CP-55940 binding to cannabinoid receptors in rat synaptosomal membranes in a concentration-dependent manner. This is the first report of a substance present endogenously in brain that can be released in a Ca(2+)-dependent manner and that binds to the cannabinoid receptor.

journal_name

J Neurochem

authors

Evans DM,Johnson MR,Howlett AC

doi

10.1111/j.1471-4159.1992.tb09787.x

subject

Has Abstract

pub_date

1992-02-01 00:00:00

pages

780-2

issue

2

eissn

0022-3042

issn

1471-4159

journal_volume

58

pub_type

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