Possible involvement of Ca++ ions, protein kinase C and Na(+)-H+ antiporter in insulin-induced endogenous dopamine release from tuberoinfundibular neurons.
Insulin (63 microM) stimulated endogenous dopamine (DA) release from tuberoinfundibular neurons. This effect was independent on the presence of extracellular glucose and did not involve the outward transport of DA, mediated by its membrane carrier. By contrast this effect was completely prevented by the removal of extracellular Ca++ ions in presence of the Ca(++)-chelator ethyleneglycol-2-(2-aminoethyl)-tetracetic acid (EGTA). Furthermore 1-(5-isoquinolinyl-sulfonyl)-2-methyl-piperazine (H7), a compound which behaves as a putative inhibitor of protein kinase C (PK-C) (10 microM), completely counteracted the stimulation of endogenous DA release induced by insulin. Amiloride (300 microM) and its 5-amino nitrogen atom-substituted derivative, 5-(N-methyl-N-(guanidinocarbonylmethyl) amiloride (MGCMA) (10 microM), a highly selective inhibitor of the Na(+)-H+ membrane antiporter, were both able to prevent the stimulatory action exerted by insulin on endogenous DA release. Collectively, these results suggest that the transductional events by which insulin stimulated endogenous DA release from TIDA neurons may involve the activation of PK-C, the enhancement of Ca++ influx and the stimulation of the Na(+)-H+ exchange system.
Amoroso
S
S
Institute of Pharmacology, 2nd School of Medicine, University of Naples, Italy.
Taglialatela
M
M
Canzoniero
L M
LM
Cragoe
E J
EJ
di Renzo
G
G
Annunziato
L
L
D000584:Amiloride / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D005260:Female; D005947:Glucose / Q000494:pharmacology; D007031:Hypothalamus / Q000378:metabolism*; D007328:Insulin / Q000494:pharmacology*; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D009474:Neurons / Q000378:metabolism*; D009627:Nomifensine / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism; D051381:Rats; D017923:Sodium-Hydrogen Exchangers
D002352:Carrier Proteins; D007328:Insulin; D017923:Sodium-Hydrogen Exchangers; D009627:Nomifensine; D007334:Insulin-Like Growth Factor I; D000584:Amiloride; D011493:Protein Kinase C; D005947:Glucose; D002118:Calcium; D004298:Dopamine