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DOPAMINE‐SENSITIVE ADENYLATE CYCLASE FROM THE RAT CAUDATE NUCLEUS: REGULATION BY GUANYL NUCLEOTIDES AND THE INTERACTION OF MAGNESIUM AND MAGNESIUM ATP 1
Author(s) -
ClementCormier Yvonne C.,
Rudolph Frederick B.,
Robison G. Alan
Publication year - 1978
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 - 10.1111/j.1471-4159.1978.tb12412.x
Subject(s) - caudate nucleus , dopamine , gtp' , cyclase , chemistry , adenylate kinase , medicine , endocrinology , dopaminergic , biochemistry , biology , enzyme
— An adenylate cyclase present in the caudate nucleus of the rat brain, which is selectively stimulated by low concentrations of dopamine and which is believed to mediate dopaminergic synaptic transmission has been characterized with respect to interactions with guanyl nucleotides and magnesium ions. The addition of GTP (10 −5 M) or GMPPNP (10 −5 M) did not alter the linear increase in cyclic AMP as a function of time in the presence and absence of dopamine. GTP did, however, inhibit basal adenylate cyclase activity in homogenates of the caudate but the dopamine‐stimulated enzyme activity was not affected, thus increasing the percent stimulation produced by dopamine. This ability of GTP to increase responsiveness to dopamine was not dependent on the level of added Mg 2+ in the assay medium. Conversely, GMPPNP (10 −5 M) markedly lowered the basal as well as the dopamine stimulated activity as a function of magnesium in the caudate. These results suggest an important role for GTP and Mg 2+ in the regulation of caudate adenylate cyclase and its activation by dopamine. In homogenates of the cortex the most dramatic effect of GTP and GMPPNP was on the potentiation of the norepinephrine effect. The guanyl nucleotides studied in the cortex did not have the inhibitory effect on basal enzyme activity as observed in homogenates of the caudate. Interactions between Mg 2+ and MgATP 2‐ and the dopamine‐sensitive adenylate cyclase from the rat caudate nucleus have also been studied. The data are consistent with a bireactant sequential mechanism where Mg 2+ is a required activator and free ATP 4 is not a significant inhibitor of the reaction. The data show that dopamine lowered the apparent K m for free Mg 2+ about 2‐fold without significantly changing the V max . GTP and GMPPNP did not alter the apparent K m for Mg 2+ but did lower the V max both in the presence and absence of dopamine. GMPPNP was more potent than GTP in producing these effects in the striatal enzyme. The data presented herein implicate an important role for guanyl nucleotides and Mg 2+ in the regulation of brain adenylate cyclase and its activation by various neurotransmitters. Furthermore, the results also suggest that although the role for guanyl nucleotides may be equally important in various areas of the brain, the mechanisms of action of guanyl nucleotides in these areas may differ.