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RESEARCH PRODUCT
The phototransduction cascade in the isolated chick pineal gland revisited.
Heike HolthuesLutz Vollrathsubject
medicine.medical_specialtyLight Signal TransductionArylamine N-AcetyltransferasePhosphodiesterase 3BiologyNitric OxidePineal GlandRetinachemistry.chemical_compoundPineal glandOrgan Culture TechniquesInternal medicinemedicineCyclic AMPAnimalsCyclic adenosine monophosphateNitric Oxide DonorsEnzyme InhibitorsMolecular BiologyCyclic guanosine monophosphateCyclic GMPMelatoninCyclic Nucleotide Phosphodiesterases Type 6Phosphoric Diester HydrolasesGeneral NeurosciencePhosphodiesteraseNatriuretic Peptide C-TypeCyclic Nucleotide Phosphodiesterases Type 3Circadian RhythmCalcium Channel Agonistsmedicine.anatomical_structureEndocrinologychemistry3'5'-Cyclic-AMP PhosphodiesterasesNeurology (clinical)PDE10ACalcium ChannelsZaprinastChickensPhotic StimulationDevelopmental BiologyEndocrine glanddescription
It is well established that the isolated chick pineal gland is directly light sensitive and that melatonin synthesis of the gland can be inhibited by exposing the gland to light during scotophase. Since not all the steps of the phototransduction cascade have been clarified to the same extent as in the retina, we have treated isolated chick pineal glands with 90 min of light during scotophase and with drugs that affect key-components of vertebrate phototransduction, i.e., cyclic guanosine monophosphate (cGMP) phosphodiesterase 6 (PDE6), cGMP levels and cGMP-gated calcium channels. The endpoint measured was the activity of the rate-limiting enzyme of melatonin synthesis, arylalkylamine N-acetyltransferase (AA-NAT), which is inhibited by light. The effects on AA-NAT activity of light were negated by addition of dipyridamol and zaprinast, either of which inhibits the light-induced activation of PDE6. The effect of light was also counteracted by the nitric oxide donor sodium nitroprusside and C-type natriuretic peptide, both of which increase cGMP levels, and by the calcium channel agonist Bay K 8644, which prevents the cGMP-decrease-induced closure of cGMP-gated calcium channels. Inhibition of nitric oxide synthase (NOS) by N(G)-nitro-l-arginine did not influence the inhibitory effect of light, suggesting that the NOS pathway does not play a role. Since the light effect on AA-NAT activity involves both cGMP and cyclic adenosine monophosphate (cAMP) hydrolysis, we have also studied whether the cGMP-inhibited cAMP phosphodiesterase 3 (PDE3) is involved. As the specific PDE3 inhibitor cilostamide is without effect, we assume that the light-induced decrease of cAMP levels does not involve PDE3. These results taken together strongly suggest that the investigated steps of the phototransduction cascade in the isolated chick pineal gland are basically similar to those in the retina.
year | journal | country | edition | language |
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2003-11-21 | Brain research |