Gα(i/o)-coupled receptor-mediated sensitization of adenylyl cyclase: 40 years later

Heterologous sensitization of adenylyl cyclase (also referred to as superactivation, sensitization, or supersensitization of adenylyl cyclase) is a cellular adaptive response first described 40 years ago in the laboratory of Dr. Marshall Nirenberg. This apparently paradoxical cellular response occurs following persistent activation of Gαi/o-coupled receptors and causes marked enhancement in the activity of adenylyl cyclases, thereby increasing cAMP production. Since our last review in 2005, significant progress in the field has led to a better understanding of the relevance of, and the cellular biochemical processes that occur during the development and expression of heterologous sensitization. In this review we will discuss the recent advancements in the field and the mechanistic hypotheses on heterologous sensitization.