The stimulatory effect of mu‐ and delta‐opioid receptors on bovine pinealocyte melatonin synthesis

Oct 16, 2004Journal of pineal research

How mu- and delta-opioid receptors increase melatonin production in cow pineal cells

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Abstract

Both the mu-opioid receptor agonist DAMGO and the delta-opioid receptor agonist DPDPE stimulated NAT activity and increased melatonin levels in cultured bovine pinealocytes.

Opioid receptors in bovine pinealocytes are involved in regulating melatonin synthesis.
Activation of mu- and delta-opioid receptors enhances the activity of the enzyme N-acetyltransferase (NAT).
The increase in melatonin levels from opioid receptor activation may be linked to higher cyclic AMP production.
The kappa-opioid receptor agonist U69593 did not affect NAT activity or melatonin secretion.
The effects of DAMGO and DPDPE were blocked by naloxone, indicating a specific opioid receptor-mediated mechanism.

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Mammalian pinealocytes synthesize and secrete melatonin. The synthesis of melatonin is regulated by several biogenic amine, amino acid and peptide transmitters. In our previous study, the delta- and mu-opioid receptors have been identified and characterized in bovine pinealocytes. In order to elaborate the function of different types of opioid receptors in regulating melatonin synthesis, we used a selective mu-opioid receptor agonist, Tyr-[D-Ala(2), N-methyl-phe(4), glycol(5)] (DAMGO), a selective delta-opioid receptor agonist, Enkephalin [D-Pen(2), D-Pen(5)], (DPDPE) and a selective kappa-opioid receptor agonist, ((+)-(5alpha, 7alpha, 8beta)-N-methyl-N-[7- (1-pyrrolidinyl)-1-oxaspiro [4,5] dec-8-yl]-benzene acetamide) (U69593) to investigate the activity of N-acetyltransferase (NAT) activity and melatonin secretion. The results of the present study show that both DAMGO and DPDPE stimulated NAT activity and increased the level of melatonin in cultured bovine pinealocytes. These stimulatory effects were blocked by naloxone, an opioid receptor antagonist. However, the kappa-opioid receptor agonist U69593 was unable to alter either the activity of NAT or the level of melatonin. In order to clarify the mechanism of how the activation of mu- and delta-opioid receptors in bovine pinealocytes leads to an increase in NAT activity, cyclic AMP levels were measured after bovine pinealocytes were treated with morphine, DAMGO and DPDPE. The results indicated that these stimulatory effects acted via induction of cAMP production. This study reveals that the stimulatory effect of opioid receptor on melatonin synthesis is mediated via the activation of adenylate cyclase system.

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The stimulatory effect of mu‐ and delta‐opioid receptors on bovine pinealocyte melatonin synthesis

Abstract

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