Title

Direct activation of M1 muscarinic receptors by the positive allosteric modulator, BQCA

Presenter Information

Katherine Brinker

Department

Biological Sciences

Major

Psychology

Research Advisor

Aronstam, Robert

Advisor's Department

Biological Sciences

Abstract

BQCA (Benzyl quinolone carboxylic acid) was recently identified as a positive allosteric modulator of the M1 muscarinic receptor. We studied the nature of this effect on muscarinic signaling at the single cell level in Chinese Hamster Ovary (CHO) cells stably transfected with cDNA clones for muscarinic receptors (M1, M3, and M5). BQCA was found to potentiate response of CHO cells expressing M1, but not M3, receptors for a low concentration (10 nM) of the agonist carbamylcholine, while a small potentiating effect on M5 was observed. Unexpectedly, BQCA activated M1 receptors in the absence of an allosteric agonist. The orthostatic antagonist atropine completely blocked allosteric receptor activation. There was no relation between direct allosteric activation by BQCA and subsequent allosteric potentiation, i.e., cells that BQCA did not activate were still subject to allosteric potentiation. Moreover, activation by BQCA did not predict the pattern of the response to agonist activation.

Biography

Katherine Brinker is a senior in psychology, is minoring in both physics and mathematics, and is pursuing research in the biology department. She will be graduating in May, and will be pursuing a Masters of Science in Business Analytics at Arizona State University in the fall.

Research Category

Sciences

Presentation Type

Poster Presentation

Document Type

Poster

Location

Upper Atrium/Hall

Presentation Date

16 Apr 2014, 9:00 am - 11:45 am

This document is currently not available here.

Share

COinS
 
Apr 16th, 9:00 AM Apr 16th, 11:45 AM

Direct activation of M1 muscarinic receptors by the positive allosteric modulator, BQCA

Upper Atrium/Hall

BQCA (Benzyl quinolone carboxylic acid) was recently identified as a positive allosteric modulator of the M1 muscarinic receptor. We studied the nature of this effect on muscarinic signaling at the single cell level in Chinese Hamster Ovary (CHO) cells stably transfected with cDNA clones for muscarinic receptors (M1, M3, and M5). BQCA was found to potentiate response of CHO cells expressing M1, but not M3, receptors for a low concentration (10 nM) of the agonist carbamylcholine, while a small potentiating effect on M5 was observed. Unexpectedly, BQCA activated M1 receptors in the absence of an allosteric agonist. The orthostatic antagonist atropine completely blocked allosteric receptor activation. There was no relation between direct allosteric activation by BQCA and subsequent allosteric potentiation, i.e., cells that BQCA did not activate were still subject to allosteric potentiation. Moreover, activation by BQCA did not predict the pattern of the response to agonist activation.