RT Journal Article SR Electronic T1 Characterization of CB1 Cannabinoid Receptors Using Receptor Peptide Fragments and Site-Directed Antibodies JF Molecular Pharmacology JO Mol Pharmacol FD American Society for Pharmacology and Experimental Therapeutics SP 504 OP 510 DO 10.1124/mol.53.3.504 VO 53 IS 3 A1 Allyn C. Howlett A1 Chao Song A1 Barbara A. Berglund A1 Gerald H. Wilken A1 J. Jill Pigg YR 1998 UL http://molpharm.aspetjournals.org/content/53/3/504.abstract AB The mechanism by which CB1 cannabinoid receptors are coupled to the Gi/Go class of G proteins was studied. A peptide representing the juxtamembrane carboxyl terminus robustly stimulated guanosine-5′-O-(3-thio)triphosphate binding. Peptides simulating subdomains of the third intracellular loop (IL3) activated minimally when present alone but produced additive effects when present in combination. Peptides representing the amino-side IL3 and the juxtamembrane carboxyl terminus autonomously inhibited adenylate cyclase, and this response was not significantly augmented or inhibited by peptides representing other intracellular domains. Site-directed antipeptide antibodies developed against the domains of the amino terminus, first extracellular loop, amino-side IL3, and juxtamembrane carboxyl terminus of CB1 receptors failed to influence binding of [3H]CP-55940. However, IgG raised against the amino-side IL3 diminished the agonist-dependent inhibition of adenylate cyclase. These experiments suggest that the juxtamembrane carboxyl terminus is critical for G protein activation by CB1 cannabinoid receptors and that the amino-side IL3 also may interact with Gi proteins leading to inhibition of adenylate cyclase.