Insulin dose-dependently inhibited tyrosine hydroxylase (TH) activity and increased intra-synaptosomal pH (pH(i)) in rat striatal nerve endings. Both these effects of insulin on TH and pH(i) 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 (pH(o)), the pH(i) 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 pH(i) 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.
CYTOPLASMIC ALKALINIZATION INDUCED BY INSULIN THROUGH AN ACTIVATION OF NA+-H+ ANTIPORTER INHIBITS TYROSINE-HYDROXYLASE ACTIVITY IN STRIATAL SYNAPTOSOMES
TAGLIALATELA, Maurizio;
1991-01-01
Abstract
Insulin dose-dependently inhibited tyrosine hydroxylase (TH) activity and increased intra-synaptosomal pH (pH(i)) in rat striatal nerve endings. Both these effects of insulin on TH and pH(i) 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 (pH(o)), the pH(i) 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 pH(i) 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.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
