Title

Subtype-specific Interactions of Oxotremorine-M with Muscarinic Acetylcholine Receptors

Presenter Information

Melissa Cambre

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

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Apr 15th, 9:00 AM Apr 15th, 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.