Guanine nucleotides regulate the affinity of melatonin receptors on the ovine pars tuberalis.
The effect of guanine nucleotides and related analogues on the binding of 2-[125I]-melatonin to membranes prepared from ovine pars tuberalis was studied. Dose-dependent inhibition of 2-[125I]-melatonin binding was observed, with an order of potency of GTP gamma S much greater than Gpp(NH)p greater than GTP = GDP. GMP, cyclic GMP and ATP had negligible effects. Analysis of saturable binding revealed that GTP gamma S (1 microM) promoted an apparent reduction in receptor density of about 50%, without a concomitant change in receptor affinity. These results are consistent with a melatonin receptor existing in an equilibrium between high- and low-affinity states, with GTP and related analogues able to cause a shift in the equilibrium in favour of the lower-affinity form. The sensitivity of 2-[125I]-melatonin binding to guanine nucleotides implies the presence of a melatonin receptor on the ovine pars tuberalis, the action of which is mediated via a G protein.
Morgan
P J
PJ
Rowett Research Institute, Aberdeen, UK.
Lawson
W
W
Davidson
G
G
Howell
H E
HE
D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D006150:Guanine Nucleotides / Q000494:pharmacology*; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D006153:Guanosine Diphosphate / Q000494:pharmacology; D006160:Guanosine Triphosphate / Q000494:pharmacology; D006165:Guanylyl Imidodiphosphate / Q000494:pharmacology; D008550:Melatonin / Q000378:metabolism; D010903:Pituitary Gland, Anterior / Q000378:metabolism*; D044094:Receptors, Melatonin; D017981:Receptors, Neurotransmitter / Q000378:metabolism*; D012756:Sheep; D013873:Thionucleotides / Q000494:pharmacology
D006150:Guanine Nucleotides; D044094:Receptors, Melatonin; D017981:Receptors, Neurotransmitter; D013873:Thionucleotides; D006153:Guanosine Diphosphate; D006165:Guanylyl Imidodiphosphate; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D006160:Guanosine Triphosphate; D008550:Melatonin