Release of phosphodiesterase activator from particulate fractions of cerebellum and striatum by putative neurotransmitters

Abstract

The endogenous phosphodiesterase activator (PDEA) described by Cheung (1,2) is, in part, stored as a membrane-bound protein (12,13). PDEA can be released from the membranes by a cAMP-dependent phosphorylation of a protein that may function as PDEA binding site (13). We found that PDEA can be released from brain particulate fraction by 1 μM norepinephrine, dopamine, adenosine, and histamine in the presence of ATP and a purified cAMP-dependent protein kinase; in similar conditions, serotonin is ineffective in concentrations up to 0.1 mM. Norepinephrine and dopamine activate the adenylate cyclase activity of those preparations from which they release the PDEA. Norepinephrine is more potent than dopamine in releasing PDEA from the particulate fraction of cerebellum, whereas dopamine is more active than norepinephrine in releasing PDEA from the particulate fraction of striatum. The release of PDEA elicited by both neurotransmitters is concentration-dependent; increasing the transmitter concentrations above a certain limit decreases the rate of PDEA release.