Sodium and potassium regulation of guanine nucleotide-stimulated adenylate cyclase in brain.
The present study examines the influence of potassium and sodium ions on guanine nucleotide regulation of adenylate cyclase in various brain regions, including the locus coeruleus (LC), dorsal raphe (DR), ventral tegmentum (VT), hippocampus (HP), frontal cortex (FC), substantia nigra (SN), neostriatum (NS) and cerebellum (CB). Guanine nucleotide regulation of adenylate cyclase was highest in the LC, DR and VT and lowest in NS and CB. Sodium and potassium ions were found to stimulate basal or GTP-activated adenylate cyclase in NS and SN, whereas the cations were found to specifically inhibit guanine nucleotide-stimulated enzyme activity in all other brain regions with the exception of CB, where there was no effect. With regard to stimulation of adenylate cyclase, lithium was more potent than sodium which was more potent than potassium in SN and NS. With regard to inhibition of the enzyme, potassium was equipotent to lithium which was greater than sodium in the other brain regions examined. Both stimulatory and inhibitory effects of cations in the different regions were significant (P less than 0.05) at 30 mM and were maximal at 90-120 mM. Sodium ion inhibition of GTP-stimulated adenylate cyclase in LC and DR was partially blocked by pertussis toxin treatment, whereas cation stimulation in NS was not affected by the toxin. The results demonstrate marked region-specific effects of sodium and potassium on adenylate cyclase, which could occur at either G-proteins or the catalytic unit of the enzyme. The possibility that ion fluxes alter G-protein function is discussed.
Duman
R S
RS
Department of Psychiatry, Yale University School of Medicine, New Haven, CT.
Terwilliger
R Z
RZ
Nestler
E J
EJ
Tallman
J F
JF
D037361:Adenylate Cyclase Toxin; D000067956:Adenylyl Cyclase Inhibitors; D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000201:enzymology* / Q000378:metabolism; D002412:Cations; D004305:Dose-Response Relationship, Drug; D019204:GTP-Binding Proteins / Q000378:metabolism; D006160:Guanosine Triphosphate / Q000502:physiology*; D066298:In Vitro Techniques; D008297:Male; D037342:Pertussis Toxin; D011188:Potassium / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D017981:Receptors, Neurotransmitter / Q000187:drug effects; D012964:Sodium / Q000494:pharmacology*; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D037361:Adenylate Cyclase Toxin; D000067956:Adenylyl Cyclase Inhibitors; D002412:Cations; D017981:Receptors, Neurotransmitter; D010566:Virulence Factors, Bordetella; D006160:Guanosine Triphosphate; D012964:Sodium; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins; D000262:Adenylyl Cyclases; D011188:Potassium