The sterol-binding antibiotic nystatin differentially modulates ligand binding of the bovine hippocampal serotonin1A receptor.
We have monitored the ligand binding of the bovine hippocampal 5-HT1A receptor following treatment with the sterol-binding antifungal antibiotic nystatin. Nystatin considerably inhibits the specific binding of the antagonist to 5-HT1A receptors in a concentration-dependent manner. However, the specific agonist binding does not show significant changes. Fluorescence polarization measurements of membrane probes incorporated at different locations in the membrane revealed a substantial decrease in the membrane order in the interior of the bilayer. Experiments with cholesterol-depleted membranes indicate that the action of nystatin is mediated through membrane cholesterol. These results represent the first report on the effect of a cholesterol-perturbing agent on the ligand-binding activity of this important neurotransmitter receptor.
Pucadyil
Thomas J
TJ
Centre for Cellular and Molecular Biology, Uppal Road, Hyderabad 500 007, India.
Shrivastava
Sandeep
S
Chattopadhyay
Amitabha
A
D000818:Animals; D002417:Cattle; D002784:Cholesterol / Q000378:metabolism*; D006624:Hippocampus / Q000378:metabolism*; D008024:Ligands; D009761:Nystatin / Q000378:metabolism / Q000494:pharmacology*; D011485:Protein Binding; D044282:Receptor, Serotonin, 5-HT1A / Q000378:metabolism*
D008024:Ligands; D044282:Receptor, Serotonin, 5-HT1A; D009761:Nystatin; D002784:Cholesterol