ชื่อวิทยานิพนธ์ THE ROLE OF OPIOID RECEPTORS IN BOVINE PINEAL
GLAND
เลขทะเบียน
06
ชื่อผู้วิจัย UAYART
CHUCHUEN
วันเดือนปีที่ทำวิจัยสำเร็จ 2003
สถาบันวิจัย MAHIDOL UNIVERSITY
บทคัดย่อ
Mammalian
pinealoecytes are neuroendocrine cells of the pineal gland that synthesize and
secrete melatonin into the blood circulation. The synthesis of melatonin is
regulated by several biogenic amine, amino acid and peptide transmitter. In a
previous study, the delta and mu opioid receptors have been identified and
characterized in bovine pinealocytes by radioligand binding technique. In order
to further clarify the existence of these receptors, the level of mRNA were
determined. By using reverse transcriptase polymerase chain reaction (RT-PCR)
followed by nest-PCR, a segment of mu-opioid receptor was amplified from mRNA of
the bovine pineal gland and cerebral cortex. In order to further elaborate the
function of different types of opioid receptors in the pineal gland, the second
objective of this study was to study the roles of opioid receptors in
regulating melatonin synthesis. We used a selective mu-opioid receptor agonist
(DAMGO), a selective delta opioid-recetor
agonist (DPDPE) and a selective kappa-opioid receptor agonist to
investigate the activity of N-acetyltransferase activity and melatonin secretion. The results of this study showed
that both DAMGO and DPDPE stimulated N-acetyItransferase 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
N-acetyItransferase or the level of melatonin. This view supported our previous
results of the existence of mu-and delta-but not kappa-opioid receptors in
bovine pinealcytes. The study of the mechanism of how the activation of opioid
receptor in pinealocytes leads to an increase in NAT activity is needed. The
third objective is to study the accumulation of cyclic AMP by using [125 I]
radioimmuno assay. Cyclic AMP levels were measured after pinealocytes were
treated with morphine, DAMGO and DPDPE. The results indicated that these
stimulatory effects acted via induction of cAMP product. This study reveals
that the stimulatory effect of opioid receptors on melatonin synthesis is mediated
via cAMP. Furthermore, the analgesic effect of melatonin and opioid on
modulation of nociception was studied by using a mode of tailflick and formalin
test. The results of this study showed that melatonin increase significantly
tail-flick latency and decreased the lifting and licking response behavior but
not scratching response behavior. These results suggest that melatonin has an
analgesic effect. Therefore, the present data provides information for future
research in searching highly efficacious melatonin analogues capable of
providing maximum analgesia and being devoid of addiction liability.
