Effect of local anesthetics on serotonin1Areceptor function.
The fundamental mechanism behind the action of local anesthetics is still not clearly understood. Phenylethanol (PEtOH) is a constituent of essential oils with a pleasant odor and can act as a local anesthetic. In this work, we have explored the effect of PEtOH on the function of the hippocampal serotonin1Areceptor, a representative neurotransmitter receptor belonging to the G protein-coupled receptor (GPCR) family. Our results show that PEtOH induces reduction in ligand binding to the serotonin1Areceptor due to lowering of binding affinity, along with a concomitant decrease in the degree of G-protein coupling. Analysis of membrane order using the environment-sensitive fluorescent probe DPH revealed decrease in membrane order with increasing PEtOH concentration, as evident from reduction in rotational correlation time of the probe. Analysis of results obtained shows that the action of local anesthetics could be attributed to the combined effects of specific interaction of the receptor with anesthetics and alteration of membrane properties (such as membrane order). These results assume relevance in the perspective of anesthetic action and could be helpful to achieve a better understanding of the possible role of anesthetics in the function of membrane receptors.
CSIR-Indian Institute of Chemical Technology, Uppal Road, Hyderabad 500 007, India; Academy of Scientific and Innovative Research, New Delhi, India.
Bhagyashree D
BD
Rao
CSIR-Centre for Cellular and Molecular Biology, Uppal Road, Hyderabad 500 007, India.
Sandeep
S
Shrivastava
CSIR-Centre for Cellular and Molecular Biology, Uppal Road, Hyderabad 500 007, India; Academy of Scientific and Innovative Research, New Delhi, India. Electronic address: amit@ccmb.res.in.
Amitabha
A
Chattopadhyay
D000779:Anesthetics, Local / Q000494:pharmacology*; D000818:Animals; D002417:Cattle; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D010626:Phenylethyl Alcohol / Q000494:pharmacology*; D044282:Receptor, Serotonin, 5-HT1A / Q000378:metabolism*
D000779:Anesthetics, Local; D044282:Receptor, Serotonin, 5-HT1A; D019204:GTP-Binding Proteins; D010626:Phenylethyl Alcohol
G-protein coupling; Hippocampal membranes; Local anesthetics; Membrane order; Phenylethanol; Serotonin(1A) receptor