Melatonin biosynthesis in photoreceptor-enriched chick retinal cell cultures: role of cyclic AMP in the K(+)-evoked, Ca(2+)-dependent induction of serotonin N-acetyltransferase activity

Neurochem Int. 1995 Aug;27(2):147-55. doi: 10.1016/0197-0186(95)00035-7.


The roles of cyclic AMP and calcium in the regulation of serotonin N-acetyltransferase (NAT) activity were studied in low density monolayer cultures of chick retinal photoreceptors and neurons. Photoreceptor-enriched retinal cell cultures were prepared from embryonic day 6 retinas and cultured for 6 days. NAT activity in these cultures could be induced by treatment with cyclic AMP protagonists, 8Br-cyclic AMP, forskolin, and 3-isobutyl-1-methylxanthine (IBMX), or by treatment with depolarizing concentrations of extracellular K+. The stimulatory effect of K+, which involves Ca2+ influx through dihydropyridine-sensitive channels, was mediated at least in part by cyclic AMP, as indicated by the following observations. Depolarizing concentrations of K+ stimulated the formation of cyclic AMP, and the stimulatory effects of K+ on both cyclic AMP formation and on NAT activity were synergistically potentiated by the cyclic nucleotide phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (IBMX). MDL 12,330A, a putative adenylate cyclase inhibitor, inhibited K(+)-evoked cyclic AMP accumulation and induction of NAT activity over the identical concentration range. In contrast, MDL 12,300A failed to inhibit the induction of NAT elicited by 8Br-cyclic AMP. H-89, an inhibitor of cyclic AMP-dependent protein kinase, antagonized the induction of NAT activity by either forskolin or K+ with equal potency for both stimuli. These results suggest that cyclic AMP plays an essential role in the induction of NAT activity that occurs as a consequence of membrane depolarization. Cyclic AMP and Ca2+ may also interact at a step distal to adenylate cyclase.(ABSTRACT TRUNCATED AT 250 WORDS)

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 1-Methyl-3-isobutylxanthine / pharmacology
  • Adenylyl Cyclases / drug effects
  • Animals
  • Arylamine N-Acetyltransferase / metabolism*
  • Calcium / physiology*
  • Cells, Cultured
  • Chick Embryo
  • Cyclic AMP / physiology*
  • Cyclic AMP-Dependent Protein Kinases / metabolism
  • Enzyme Activation
  • Enzyme Induction
  • Ion Channel Gating
  • Melatonin / biosynthesis*
  • Membrane Potentials / physiology
  • Photoreceptor Cells / cytology
  • Photoreceptor Cells / metabolism*
  • Potassium / physiology*


  • Cyclic AMP
  • Arylamine N-Acetyltransferase
  • Cyclic AMP-Dependent Protein Kinases
  • Adenylyl Cyclases
  • Melatonin
  • Potassium
  • Calcium
  • 1-Methyl-3-isobutylxanthine