Guanosine 5'-O-(3-thiotriphosphate) and cations regulate melatonin receptors, and melatonin inhibits cyclic AMP production in the spinal cord.
Effects of guanosine 5'-O-(3-thiotriphosphate) (GTP gamma S) and cations on 2-[125I]iodomelatonin binding were investigated in membrane preparations of the chicken spinal cord. At concentrations of 10 and 50 mumol/l, GTP gamma S dose-dependently increased (p < 0.05) the equilibrium dissociation constant (Kd) and depressed (p < 0.05) the maximum number of binding sites (Bmax). Na+ at a concentration of 125 mmol/l significantly increased (p < 0.05) the Kd and decreased (p < 0.05) the Bmax, and Mg2+ (2.5 mmol/l) significantly increased (p < 0.05) the Bmax without changes in Kd. In addition, Na+ and Mg2+ affected the interactions of GTP gamma S with melatonin receptors. In the spinal cord explants, melatonin (10 nmol/l) attenuated forskolin-stimulated cyclic AMP production by 53.1%, and preincubation with pertussis toxin abolished this effect of melatonin. These results suggest that the melatonin receptors in the chicken spinal cord are linked to its second messenger via a pertussis-toxin-sensitive guanine-nucleotide-binding protein, and that cations modulate these receptors. Our studies further support a previous hypothesis that melatonin exerts a direct action on spinal cord functions.
Wan
Q
Q
Department of Physiology, University of Hong Kong, Hong Kong.
Liao
M X
MX
Pang
C S
CS
Pang
S F
SF
Brown
G M
GM
D000818:Animals; D002412:Cations / Q000494:pharmacology; D002645:Chickens; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000096:biosynthesis*; D005260:Female; D019204:GTP-Binding Proteins / Q000378:metabolism; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000494:pharmacology*; D066298:In Vitro Techniques; D007700:Kinetics; D008274:Magnesium / Q000494:pharmacology; D008297:Male; D008550:Melatonin / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology*; D008959:Models, Neurological; D011956:Receptors, Cell Surface / Q000187:drug effects* / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000187:drug effects* / Q000378:metabolism; D044094:Receptors, Melatonin; D015290:Second Messenger Systems / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D012964:Sodium / Q000494:pharmacology; D013116:Spinal Cord / Q000187:drug effects* / Q000378:metabolism*
D002412:Cations; D011956:Receptors, Cell Surface; D018160:Receptors, Cytoplasmic and Nuclear; D044094:Receptors, Melatonin; D005576:Colforsin; D016244:Guanosine 5'-O-(3-Thiotriphosphate); C044556:2-iodomelatonin; D012964:Sodium; D000242:Cyclic AMP; D019204:GTP-Binding Proteins; D008274:Magnesium; D008550:Melatonin