Cytoplasmic alkalinization induced by insulin through an activation of Na(+)-H+ antiporter inhibits tyrosine hydroxylase activity in striatal synaptosomes.
Insulin dose-dependently inhibited tyrosine hydroxylase (TH) activity and increased intrasynaposomal pH (pHi) in rat striatal nerve endings. Both these effects of insulin on TH and pHi were prevented by the 5-(N-methyl-N-(guanidinocarbonylmethyl) amiloride (MGCMA), a putative selective inhibitor of the Na(+)-H+ antiporter. Interestingly when, by changing the extracellular pH (pHo), the pHi was increased, from 7.1 up to 7.5, an equivalent inhibition of TH activity occurred. The inhibitory action exerted from insulin on TH activity disappeared when the hormone was added to synaptosomes whose pHi was lowered to 6.83. Collectively, the results of the present study showed that insulin inhibited TH activity in striatal synaptosomes. This effect seems to involve the activation of the Na(+)-H+ antiporter. This exchange system once activated, may induce an intrasynaptosomal alkalinization, a condition in which TH activity is inhibited.
Amoroso
S
S
Department of Pharmacology, 2nd School of Medicine, University of Naples.
Di Renzo
G
G
Taglialatela
M
M
Canzoniero
L M
LM
Cragoe
E J
EJ
Annunziato
L
L
D000584:Amiloride / Q000031:analogs & derivatives; D000818:Animals; D002352:Carrier Proteins / Q000187:drug effects*; D003342:Corpus Striatum / Q000187:drug effects* / Q000201:enzymology; D003593:Cytoplasm / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006863:Hydrogen-Ion Concentration; D007328:Insulin / Q000494:pharmacology*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D017923:Sodium-Hydrogen Exchangers; D013574:Synaptosomes / Q000187:drug effects* / Q000201:enzymology; D014446:Tyrosine 3-Monooxygenase / Q000037:antagonists & inhibitors*
D002352:Carrier Proteins; D007328:Insulin; D017923:Sodium-Hydrogen Exchangers; D000584:Amiloride; D014446:Tyrosine 3-Monooxygenase