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Dinucleotide Receptor Modulation by Protein Kinases (Protein Kinases A and C) and Protein Phosphatases in Rat Brain Synaptic Terminals
Author(s) -
Pintor Jesús,
Gualix Javier,
MirasPortugal M. Teresa
Publication year - 1997
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.1471-4159.1997.68062552.x
Subject(s) - protein kinase c , okadaic acid , staurosporine , phosphatase , ionotropic effect , protein kinase a , biochemistry , kinase , dephosphorylation , phosphorylation , receptor , forskolin , biology , microbiology and biotechnology , chemistry , glutamate receptor
The diadenosine polyphosphates, diadenosine tetraphosphate and diadenosine pentaphosphate (Ap 5 A), can activate an ionotropic dinucleotide receptor that induces Ca 2+ transients into synaptosomes prepared from rat brain. This receptor, also termed the P 4 purinoceptor, is sensitive only to adenine dinucleotides and is insensitive to ATP. Studies on the modulatory role of protein kinase A (PKA), protein kinase C (PKC), and protein phosphatases on the response of diadenosine polyphosphate receptors were performed by measuring the changes in the intracellular Ca 2+ levels with fura‐2. Activation and inhibition of PKA were carried out by means of forskolin and the PKA inhibitory peptide (PKA‐IP), respectively. The Ap 5 A response was inhibited by forksolin to 35% of control values, but PKA‐IP induced an increase of 37%. The effect of PKC activation was similar to that observed for PKA. PKC stimulation with phorbol 12,13‐dibutyrate produced an inhibition of 67%, whereas the PKC inhibitors staurosporine and PKC inhibitory peptide enhanced the responses elicited by Ap 5 A to 40% in both cases. Protein phosphatase inhibitors diminished the responses elicited by Ap 5 A to 17% in the case of okadaic acid, to 50% for microcystin, and to 45% in the case of cyclosporin A. Thus, the activity of dinucleotide receptors in rat brain synaptosomes appears to be modulated by phosphorylation/dephosphorylation. These processes could be of physiological significance in the control of transmitter release from neurons that are postsynaptic to nerves that release diadenosine polyphosphates.