Effects of propranolol on catecholamine synthesis and uptake in the central nervous system of the rat.
These studies were undertaken to determine the effects of propranolol on catecholamine synthesis and uptake in the rat central nervous system. The effects of propranolol on catecholamine synthesis were studied in vitro in striatal and hypothalamic synaptosomes, and also in vivo. In addition, the effects of propranolol on catecholamine uptake in striatal and hypothalamic synaptosomes were evaluated. Propranolol inhibited synaptosomal catecholamine synthesis and uptake in both tissues. Norepinephrine uptake in the hypothalamus was most sensitive to propranolol inhibition (IC50 = 5 microM). Dopamine synthesis in striatal synaptosomes was also inhibited markedly, with an IC50 = 8 microM. After in vivo administration, propranolol decreased the accumulation of dopa in the striatum, confirming propranolol's synthesis inhibiting effect in dopaminergic terminals. Studies of soluble striatal tyrosine hydroxylase revealed that propranolol has a direct inhibitory effect on the enzyme. These results indicate that propranolol administration may cause a potentiation of norepinephrine activity specifically at alpha receptors, due to concurrent beta receptor blockade and inhibition of norepinephrine reuptake and a decrease in dopamine activity at dopaminergic receptor sites due to an inhibition of dopamine formation.
Tuross
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N
Patrick
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D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002395:Catecholamines / Q000096:biosynthesis / Q000378:metabolism*; D003342:Corpus Striatum / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006863:Hydrogen-Ion Concentration; D007031:Hypothalamus / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D011433:Propranolol / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D011919:Rats, Inbred Strains; D012559:Schizophrenia / Q000188:drug therapy; D013237:Stereoisomerism; D013574:Synaptosomes / Q000378:metabolism; D014443:Tyrosine / Q000378:metabolism; D014446:Tyrosine 3-Monooxygenase / Q000032:analysis
D014150:Antipsychotic Agents; D002395:Catecholamines; D014443:Tyrosine; D011433:Propranolol; D014446:Tyrosine 3-Monooxygenase