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Differential Requirements of Sodium for Coupling of Cannabinoid Receptors to Adenylyl Cyclase in Rat Brain Membranes
Author(s) -
Pacheco Mary A.,
Ward Susan J.,
Childers Steven R.
Publication year - 1994
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1994.62051773.x
Subject(s) - adenylyl cyclase , chemistry , cannabinoid , agonist , g protein , receptor , cannabinoid receptor , gtp' , gs alpha subunit , biochemistry , enzyme
Sodium is generally required for optimal inhibition of adenylyl cyclase by G l/o ‐coupled receptors. Canna‐binoids bind to specific receptors that act like other members of the G l/o ‐coupled receptor superfamily to inhibit adenylyl cyclase. However, assay of cannabinoid inhibition of adenylyl cyclase in rat cerebellar membranes revealed that concentrations of NaCI ranging from 0 to 150 m M had no effect on agonist inhibition. This lack of effect of sodium was not unique to cannabinoid receptors, because the same results were observed using baclofen as an agonist for GABA B receptors in cerebellar membranes. The lack of sodium dependence was region‐specific, because assay of cannabinoid and opioid inhibition of adenylyl cyclase in striatum revealed an expected sodium dependence, with 50 m M NaCI providing maximal inhibition levels by both sets of agonists. This difference in sodium requirements between these two regions was maintained at the G protein level, because agonist‐stimulated low K m GTPase activity was maximal at 50 mM NaCI in striatal membranes, but was maximal in the absence of NaCI in cerebellar membranes. Assay of [ 3 H]WIN 55212–2 binding in cerebellar membranes revealed that the binding of this labeled agonist was sensitive to sodium and guanine nucleotides like other G l/o ‐coupled receptors, because both NaCI and the nonhydrolyzable GTP analogue Gpp(NH)p significantly inhibited binding. These results suggest that differences in receptor‐G protein coupling exist for cannabinoid receptors between these two brain regions.