Subtype-specific Interactions of Oxotremorine-M with Muscarinic Acetylcholine Receptors
Department
Biological Sciences
Major
Biological Sciences
Research Advisor
Aronstam, Robert
Advisor's Department
Biological Sciences
Funding Source
Funded by the Missouri S&T cDNA Resource Center (www.cdna.org)
Abstract
There are five subtypes of muscarinic acetylcholine receptors, the product of separate genes. M1, M3 and M5 muscarinic receptors respond to agonists by activating phospholipase C activity, thereby releasing inositol trisphosphate and releasing calcium from the endoplasmic reticulum. Most agonists have very similar affinities and efficacies for these receptors. In order to identify an agonist which might affect these receptors differentially, we evaluated the effect of oxotremorine-M (oxo-M) on calcium responses mediated by these receptors expressed in CHO cells. Cytosolic calcium levels were measured by ratiometric measurements of a calcium-sensitive fluorescent dye, fura-2, by single cell imaging. Threshold responses were determined for each receptor subtype. M1 were 10 fold more sensitive to oxo-M than M5 receptors, and M5 receptors were 10 times more sensitive than M3 receptors. These findings demonstrate that oxo-M is the most receptor-selective agonist identified to date, and suggests that it may be possible to selectively stimulate muscarinic responses associated with specific physiological responses with appropriate pharmacological agents.
Biography
Melissa Cambre is a Senior Biological Sciences major. She intends on getting a Masters in Toxicology after she graduates.
Research Category
Sciences
Presentation Type
Poster Presentation
Document Type
Poster
Location
Upper Atrium/Hall
Presentation Date
15 Apr 2015, 9:00 am - 11:45 am
Subtype-specific Interactions of Oxotremorine-M with Muscarinic Acetylcholine Receptors
Upper Atrium/Hall
There are five subtypes of muscarinic acetylcholine receptors, the product of separate genes. M1, M3 and M5 muscarinic receptors respond to agonists by activating phospholipase C activity, thereby releasing inositol trisphosphate and releasing calcium from the endoplasmic reticulum. Most agonists have very similar affinities and efficacies for these receptors. In order to identify an agonist which might affect these receptors differentially, we evaluated the effect of oxotremorine-M (oxo-M) on calcium responses mediated by these receptors expressed in CHO cells. Cytosolic calcium levels were measured by ratiometric measurements of a calcium-sensitive fluorescent dye, fura-2, by single cell imaging. Threshold responses were determined for each receptor subtype. M1 were 10 fold more sensitive to oxo-M than M5 receptors, and M5 receptors were 10 times more sensitive than M3 receptors. These findings demonstrate that oxo-M is the most receptor-selective agonist identified to date, and suggests that it may be possible to selectively stimulate muscarinic responses associated with specific physiological responses with appropriate pharmacological agents.
