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This Article Full Text Full Text (PDF) All Versions of this Article: 287/1/L69    most recent 00454.2003v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via ISI Web of Science (2) Citing Articles via Google Scholar Google Scholar Articles by Sasamori, K. Articles by Hattori, T. Search for Related Content PubMed PubMed Citation Articles by Sasamori, K. Articles by Hattori, T.

Cyclic ADP-ribose, a putative Ca²⁺-mobilizing second messenger, operates in submucosal gland acinar cells

¹Divisions of ¹Respiratory and Infectious Diseases and ³³Cardiovascular Medicine, Tohoku University Graduate School of Medicine, Sendai 980-8574; and ²²Department of Biochemistry, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan

Submitted 24 December 2003 ; accepted in final form 18 February 2004

Cyclic ADP-ribose (cADPR), a putative Ca²⁺-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 Ca²⁺ release, quantification of cellular cADPR, and RT-PCR for CD38 mRNA in human and feline tracheal glands. cADPR (>6 µM), infused into the cell via the patch pipette, caused ionic currents dependent on cellular Ca²⁺. Infusions of lower concentrations (2–4 µM) 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 Ca²⁺ in response to both IP₃ and cADPR. cADPR released Ca²⁺ 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 Ca²⁺, resulting in Cl^– secretion.

patch clamp; CD38; calcium store; inositol 1,4,5-trisphosphate; calcium; acetylcholine