Agonism and antagonism in cyclic nucleotide-gated channels

环核苷酸门控通道中的激动和拮抗作用

• 批准号: 312124-2011
• 负责人: Young, Edgar
• 金额: $ 2.19万
• 依托单位: Simon Fraser University
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2012
• 资助国家: 加拿大
• 起止时间: 2012-01-01 至 2013-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=505877
• 关键词: Agonism; antagonism; cyclic; nucleotide; gated

Cells control their life processes by producing natural chemical compounds (messengers) that bind to specific receptor proteins; in response, the receptors change their molecular structure in order to activate a particular biological function. Many physiological disorders, such as cancer and heart disease which afflict millions of Canadians, could be fought by artificial messengers (drugs) that either stimulate or suppress the ON- and OFF-switching of a specific receptor. My lab studies certain receptors called ion channels whose ON-conformation produces an electric current, so we can observe ON- and OFF-switching directly. We study a number of different ion channels, all of which respond to one type of messenger called cyclic nucleotide; this messenger is generated by the body under conditions of excitation, such as the "fight-or-flight" adrenaline rush, or during epileptic seizures in some parts of the brain. The molecules that form these ion channels all contain a specific sensing-domain which is the site for binding cyclic nucleotide. This sensing-domain obviously helps ON-switching after cyclic nucleotide is bound, but our lab has discovered that in different kinds of channels, the sensing-domain can do much more! For instance, in some channels, the sensing-domain will push the receptor OFF after being ON.

细胞通过产生与特定受体蛋白结合的天然化合物(信使)来控制它们的生命过程；作为回应，受体改变它们的分子结构，以激活特定的生物功能。许多生理性疾病，如折磨着数百万加拿大人的癌症和心脏病，可以通过人工信使(药物)来对抗，这些信使或者刺激或抑制特定受体的开关。我的实验室研究某些被称为离子通道的受体，它们的通电构象会产生电流，因此我们可以直接观察通断开关。我们研究了许多不同的离子通道，所有这些通道都对一种名为环核苷酸的信使做出反应；这种信使是由身体在兴奋条件下产生的，比如肾上腺素激增，或者在大脑某些部位癫痫发作时产生。形成这些离子通道的分子都包含一个特定的感应域，它是与环核苷酸结合的部位。这个感应域显然有助于环核苷酸结合后的开启开关，但我们的实验室发现，在不同类型的通道中，感应域可以做得更多！例如，在一些通道中，感应域在开启后会将受体推开。