Characterisation of a low-affinity melatonin binding site in Syrian hamster brain
نام عام مواد
[Thesis]
نام نخستين پديدآور
D. S. Pickering
وضعیت نشر و پخش و غیره
نام ناشر، پخش کننده و غيره
McMaster University (Canada)
تاریخ نشرو بخش و غیره
1992
مشخصات ظاهری
نام خاص و کميت اثر
298
یادداشتهای مربوط به پایان نامه ها
جزئيات پايان نامه و نوع درجه آن
Ph.D.
کسي که مدرک را اعطا کرده
McMaster University (Canada)
امتياز متن
1992
یادداشتهای مربوط به خلاصه یا چکیده
متن يادداشت
The pharmacology of 2-(I) iodomelatonin ((I) MEL) binding was investigated in Syrian hamster brain regions. Both kinetic and saturation binding analysis revealed a site with an affinity of usd\approxusd2 nM in the hypothalamus. Correlation of the pharmacological profiles in different brain regions indicated this site also to be present in the cerebral cortex and hippocampus. This binding site appeared to be present throughout the CNS and peripheral tissues of the hamster and is distinct from the picomolar-affinity melatonin receptor. Using the technique of radiation inactivation, the molecular sizes of the chick retinal picomolar-affinity melatonin receptor (Mr = 44 kDa) and hamster hypothalamic low (nanomolar)-affinity binding site (Mr = 30 kDa) were found to be significantly (p < 0.04) different. This, along with the pharmacological differences, supports the notion of two separate melatonin binding sites. Binding studies indicated that the continuous cell line RPMI 1846 (Syrian hamster melanoma) possesses a melatonin binding site similar to that found in the hamster CNS. A high correlation was observed for a series of compounds between the Ki in hamster hypothalamic membranes vs RPMI 1846 membranes. Scatchard-Rosenthal analysis of saturation binding of (I) MEL to membranes indicated a site of similar affinity to that in brain. This cell line was used to study potential signal transduction mechanisms for the site. No effect of melatonin was seen on basal or forskolin-stimulated membrane adenylate cyclase activity. Using (H) adenine and (H) myo-inositol prelabelling of cells, melatonin was found to be without effect on in situ basal or stimulated cAMP or basal IP3 levels. In Ca-flux experiments, melatonin was without effect on basal or K-stimulated uptake in hamster brain synaptosomes or basal uptake in RPMI 1846 cells. This nanomolar-affinity melatonin binding site therefore does not seem to be coupled to the adenylate cyclase or inositol phosphate second messenger systems and its biochemical and physiological function(s) remain(s) unknown.
موضوع (اسم عام یاعبارت اسمی عام)
موضوع مستند نشده
Biochemistry
موضوع مستند نشده
Biological sciences
موضوع مستند نشده
Neurology
موضوع مستند نشده
Pure sciences
نام شخص به منزله سر شناسه - (مسئولیت معنوی درجه اول )