Relationship of calmodulin and dopaminergic activity in the striatum.
Increasing evidence suggests a relationship between dopaminergic activity in the striatum and the content of calmodulin (CaM), an endogenous Ca2+-binding protein. The content of CaM in striatal membranes is increased by treatments that produce supersensitivity in striatal membranes is increased by treatments that produce supersensitivity of striatal dopaminergic receptors such as chronic neuroleptic treatment or injection of 6-hydroxydopamine. Concomitant with the increase in CaM is a greater sensitivity of adenylate cyclase to dopamine and an increase in Ca2+-sensitive phosphorylation in the striatal membranes. Procedures that result in dopaminergic subsensitivity, such as amphetamine treatment, increase the cytosolic content of CaM that can subsequently activate Ca2+ and CaM-dependent phosphodiesterase activity. In vitro studies have demonstrated that CaM and Ca2+ can stimulate basal adenylate cyclase activity in a striatal particulate fraction as well as increase the sensitivity of the enzyme to dopamine. Ca2+ and CaM most likely affect the dopamine-sensitive adenylate cyclase by interacting with guanyl nucleotides, which are required for dopamine sensitivity. It is concluded that a change in CaM concentration and/or location occurs during conditions of altered dopaminergic sensitivity in the striatum. These changes in CaM coupled with potential alterations in the Ca2+ concentration could modulate the sensitivity of the dopamine system and many CaM-dependent enzymes.
D015087:2',3'-Cyclic-Nucleotide Phosphodiesterases / Q000378:metabolism; D000262:Adenylyl Cyclases / Q000378:metabolism; D000661:Amphetamine / Q000494:pharmacology; D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology; D002135:Calcium-Binding Proteins / Q000502:physiology*; D002147:Calmodulin / Q000502:physiology*; D002462:Cell Membrane / Q000378:metabolism; D003342:Corpus Striatum / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism; D051381:Rats; D011954:Receptors, Dopamine / Q000378:metabolism
D014150:Antipsychotic Agents; D002135:Calcium-Binding Proteins; D002147:Calmodulin; D011954:Receptors, Dopamine; D000661:Amphetamine; D011494:Protein Kinases; D015087:2',3'-Cyclic-Nucleotide Phosphodiesterases; D000262:Adenylyl Cyclases; D004298:Dopamine