Novel Cycling Assays for cADPR and NAADP

Abstract

An important criterion for a second messenger is that its cellular concentrations must be responsive to the first messenger. It is thus crucial that specific and sensitive assays for cADPR and NAADP be widely available for monitoring their endogenous levels under a variety of physiological conditions. The first assay for cADPR was a bioassay based on its Ca²⁺ releasing activity in sea urchin egg homogenates [1, 2]. Using this assay, it was demonstrated that cADPR was naturally occurring in many mammalian tissues [3]. Since then, a more sensitive radioimmunoassay (RIA) for cADPR has also been developed [4, 5]. With these assays, the cellular levels of cADPR have been shown to be modulated by various surface receptor agonists, including abscisic acid [6], a plant hormone, a T-cell receptor antibody [7] and acetylcholine [8]. Intriguingly, cell permeant first messengers, such as nitric oxide [9, 10] and retinoic acid [4], metabolic factors, such as glucose [11], vitamin B12 [12], and even a physical stimulus, such as heat shock [13], can elevate cADPR levels, indicating cADPR is involved in a very broad spectrum of signaling functions.