Effects of the blockade of high voltage-activated calcium channels on in vitro pineal melatonin synthesis.
The presence of high voltage-activated calcium channels in the rat pineal gland is well known. However, their role in pineal metabolism is not completely understood and is even controversial. Better to understand this matter, we investigated the effects of L-, N- or P/Q-type calcium channel blockers (nifedipine, omega-conotoxin GVIA, omega-agatoxin IVA, respectively) on melatonin content and arylalkylamine-N-acetyltransferase activity of denervated rat pineal glands kept for 48 h in culture and stimulated with norepinephrine. Melatonin was measured by high performance liquid chromatography with electrochemical detection and arylalkylamine-N-acetyltransferase activity was quantified by radiometric assay. Pre-incubation with any of these high voltage-activated calcium channel blockers reduced the melatonin production induced by norepinephrine although arylalkylamine-N-acetyltransferase activity was reduced only by the N-type calcium channel antagonist, omega-conotoxin GVIA. The results indicate that calcium influx through L-, N- or P/Q-type of high voltage-activated calcium channels is necessary for the full expression of the metabolic process leading to melatonin synthesis in the rat pineal glands. However, the mechanisms involved in this process are different for the L- or P/Q- and N-type calcium channels.
Afeche
Solange C
SC
Laboratory of Pharmacology, Butantan Institute, Av. Vital Brazil, 1500 São Paulo, SP 05503-900, Brazil. soafeche@butantan.gov.br
Barbosa
Roseli
R
Scialfa
Julieta H
JH
Terra
Ilza M
IM
Cassola
Antonio C
AC
Cipolla-Neto
José
J
D000818:Animals; D047068:Arylalkylamine N-Acetyltransferase / Q000187:drug effects / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D015220:Calcium Channels / Q000187:drug effects* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D008297:Male; D008550:Melatonin / Q000032:analysis / Q000096:biosynthesis*; D009543:Nifedipine / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D009924:Organ Culture Techniques; D010870:Pineal Gland / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D020867:omega-Agatoxin IVA / Q000494:pharmacology; D020866:omega-Conotoxin GVIA / Q000494:pharmacology
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D020867:omega-Agatoxin IVA; D020866:omega-Conotoxin GVIA; D047068:Arylalkylamine N-Acetyltransferase; D009543:Nifedipine; D008550:Melatonin; D009638:Norepinephrine