Effect of alcohols on G-protein coupling of serotonin(1A) receptors from bovine hippocampus.
The serotonin(1A) (5-hydroxytryptamine [5-HT](1A)) receptors are members of a superfamily of seven transmembrane domain receptors that couple to G-proteins. Serotonergic signalling has been shown to play an important role in alcohol intake, preference and dependence. G-protein coupling of the 5-HT(1A) receptor serves as an important determinant for serotonergic signalling. We have studied the effect of alcohols on G-protein coupling of bovine hippocampal 5-HT(1A) receptors in native membranes. This was done by monitoring the modulation of ligand (agonist and antagonist) binding in presence of alcohols by guanosine-5'-O-(3-thiotriphosphate) (GTP-gamma-S), a non-hydrolyzable analogue of GTP. Our results show that alcohols inhibit the specific binding of the agonist 8-hydroxy-2-(di-N-propylamino)tetralin (except in case of ethanol) and the antagonist 4-(2'-methoxy)-phenyl-1-[2'-(N-2"-pyridinyl)-p-fluorobenzamido]eth yl- piperazine to 5-HT(1A) receptors in a concentration-dependent manner. Further, we show here that the action of alcohols on the bovine hippocampal 5-HT(1A) receptors could be modulated by guanine nucleotides and that the mode of action of ethanol on the 5-HT(1A) receptor may be quite different than that of other alcohols. The effect of GTP-gamma-S on the agonist and the antagonist binding is found to be markedly different. Our results could be significant in the overall context of the role of G-protein coupling in serotonergic neurotransmission and its role in alcohol tolerance and dependence.
Harikumar
K G
KG
Centre for Cellular and Molecular Biology, Hyderabad, India.
Chattopadhyay
A
A
D000437:Alcoholism / Q000378:metabolism / Q000503:physiopathology; D000438:Alcohols / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D001665:Binding Sites / Q000187:drug effects / Q000502:physiology; D002417:Cattle; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000187:drug effects* / Q000378:metabolism*; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D011869:Radioligand Assay; D011985:Receptors, Serotonin / Q000187:drug effects* / Q000378:metabolism*; D044263:Receptors, Serotonin, 5-HT1; D013347:Subcellular Fractions
D000438:Alcohols; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D019204:GTP-Binding Proteins