Cyclic ADP-ribose, a putative Ca -mobilizing second messenger, operates in submucosal gland acinar cells

Sasamori, Kan, Tsukasa Sasaki, Shin Takasawa, Tsutomu Tamada, Masayuki Nara, Toshiya Irokawa, Sanae Shimura, Kunio Shirato, and Toshio Hattori. Cyclic ADP-ribose, a putative Ca -mobilizing second messenger, operates in submucosal gland acinar cells. Am J Physiol Lung Cell Mol Physiol 287: L69–L78, 2004. First published February 27, 2004; 10.1152/ajplung.00454. 2003.—Cyclic ADP-ribose (cADPR), a putative Ca -mobilizing second messenger, has been reported to operate in several mammalian cells. To investigate whether cADPR is involved in electrolyte secretion from airway glands, we used a patch-clamp technique, the measurement of microsomal Ca release, quantification of cellular cADPR, and RT-PCR for CD38 mRNA in human and feline tracheal glands. cADPR ( 6 M), infused into the cell via the patch pipette, caused ionic currents dependent on cellular Ca . Infusions of lower concentrations (2–4 M) of cADPR or inositol 1,4,5-trisphosphate (IP3) alone were without effect on the baseline current, but a combined application of cADPR and IP3 mimicked the cellular response to low concentrations of acetylcholine (ACh). Microsomes derived from the isolated glands released Ca in response to both IP3 and cADPR. cADPR released Ca from microsomes desensitized to IP3 or those treated with heparin. The mRNA for CD38, an enzyme protein involved in cADPR metabolism, was detected in human tissues, including tracheal glands, and the cellular content of cADPR was increased with physiologically relevant concentrations of ACh. We conclude that cADPR, in concert with IP3, operates in airway gland acinar cells to mobilize Ca , resulting in Cl secretion.