Tosyl-lysyl chloromethylketone inactivation of adenylate cyclase in separate regions of the rat brain.
Pretreatment of membranes from rat cerebral cortex, striatum and hippocampus with tosyl-lysyl chloromethylketone (TLCK) modified the adenylate cyclase activity. In the striatum preincubation with TLCK (0.5-6 mM), in the absence and presence of Gpp(NH)p and dopamine, dose dependently inactivated the basal activity of adenylate cyclase. In the cortex and hippocampus a biphasic action of TLCK on the basal activity of adenylate cyclase was observed. Low concentrations of TLCK (0.5-1 mM) enhanced the enzyme activity, while higher concentrations (3-6 mM) inhibited the activity. In the cortex and hippocampus this action of TLCK was found also in the presence of isoprenaline and 5-HT, respectively. In the three brain areas incubation with TLCK inactivated the basal and receptor agonist-stimulated adenylate cyclase to equal degrees. In membranes pretreated with 1 mM TLCK the enzyme activity stimulated by forskolin, Gpp(NH)p, and receptor agonists was reduced in both the striatum and hippocampus. The present results indicate that TLCK affects the catalytic unit of adenylate cyclase. The distinct actions of TLCK in the striatum compared with those in the cortex and hippocampus may suggest region-specific differences in the regulation of the catalytic unit of adenylate cyclase in the brain.
Mørk
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Department of Pharmacology, University of Copenhagen, Denmark.
Geisler
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D000067956:Adenylyl Cyclase Inhibitors; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000201:enzymology; D002540:Cerebral Cortex / Q000187:drug effects; D003342:Corpus Striatum / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D014107:Tosyllysine Chloromethyl Ketone / Q000494:pharmacology*
D000067956:Adenylyl Cyclase Inhibitors; D014107:Tosyllysine Chloromethyl Ketone