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