The inverse changes of mouse brain ornithine and S-adenosylmethionine decarboxylase activities by chlorpromazine and imipramine. Dependence of ornithine decarboxylase induction on beta-adrenoceptors.
Intraperitoneal injection of chlorpromazine and imipramine increases mouse brain ornithine decarboxylase but decreases S-adenosyl-L-methionine decarboxylase activity. Maximal effect was obtained 6-8 hr after treatment at which time single dose of chlorpromazine (50 mg/kg) stimulated ornithine decarboxylase activity 7-fold and decreased S-adenosylmethionine decarboxylase activity to 50% from the control level. Correspondingly, ornithine decarboxylase activity was 5.5 times higher than the control value and S-adenosylmethionine decarboxylase activity about 40% from that after imipramine injection (80 mg/kg). The possible dependence of the enzyme responses on adrenergic receptors was studied using alpha-adrenoceptor antagonist, phentolamine, and beta-adrenoceptor antagonist, propranolol, concurrently with chlorpromazine and imipramine. The stimulation of ornithine decarboxylase but not the inhibition of S-adenosylmethionine decarboxylase could be abolished by propranolol (10 mg/kg), whereas phentolamine (10 mg/kg) slightly increased ornithine decarboxylase activity even when given alone. This suggests that beta- but not alpha-adrenergic mediation is involved in the stimulation of mouse brain ornithine decarboxylase activity and that brain ornithine and S-adenosylmethionine decarboxylase activities are independently regulated. When chlorpromazine and imipramine were tested in vitro, both of them turned out to have an inhibitory effect on S-adenosylmethionine decarboxylase. The former caused 50% inhibition at a concentration of 1 mM and the latter at 2 mM. Preliminary tests suggest that the type of inhibition is noncompetitive for both of them.
D012437:Adenosylmethionine Decarboxylase / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000201:enzymology*; D002262:Carboxy-Lyases / Q000378:metabolism*; D002746:Chlorpromazine / Q000494:pharmacology*; D004790:Enzyme Induction / Q000187:drug effects; D007099:Imipramine / Q000494:pharmacology*; D051379:Mice; D008815:Mice, Inbred Strains; D009955:Ornithine Decarboxylase / Q000096:biosynthesis / Q000378:metabolism*; D010646:Phentolamine / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D011941:Receptors, Adrenergic / Q000502:physiology*; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000502:physiology*
D011941:Receptors, Adrenergic; D011943:Receptors, Adrenergic, beta; D011433:Propranolol; D002262:Carboxy-Lyases; D009955:Ornithine Decarboxylase; D012437:Adenosylmethionine Decarboxylase; D007099:Imipramine; D002746:Chlorpromazine; D010646:Phentolamine