Cyclic ADP-ribose, a putative Ca2+-mobilizing second messenger, operates in submucosal gland acinar cells.
Cyclic ADP-ribose (cADPR), a putative Ca(2+)-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(2+) release, quantification of cellular cADPR, and RT-PCR for CD38 mRNA in human and feline tracheal glands. cADPR (>6 microM), infused into the cell via the patch pipette, caused ionic currents dependent on cellular Ca(2+). Infusions of lower concentrations (2-4 microM) of cADPR or inositol 1,4,5-trisphosphate (IP(3)) alone were without effect on the baseline current, but a combined application of cADPR and IP(3) mimicked the cellular response to low concentrations of acetylcholine (ACh). Microsomes derived from the isolated glands released Ca(2+) in response to both IP(3) and cADPR. cADPR released Ca(2+) from microsomes desensitized to IP(3) 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 IP(3), operates in airway gland acinar cells to mobilize Ca(2+), resulting in Cl(-) secretion.
Division of Respiratory and Infectious Diseases, Tohoku University Graduate School of Medicine, Sendai, Japan. sasamori@int1.med.tohoku.ac.jp
Kan
K
Sasamori
Tsukasa
T
Sasaki
Shin
S
Takasawa
Tsutomu
T
Tamada
Masayuki
M
Nara
Toshiya
T
Irokawa
Sanae
S
Shimura
Kunio
K
Shirato
Toshio
T
Hattori
D036541:ADP-ribosyl Cyclase / Q000235:genetics; D051997:ADP-ribosyl Cyclase 1; D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D015703:Antigens, CD / Q000235:genetics; D002118:Calcium / Q000378:metabolism*; D002415:Cats; D018118:Chloride Channels / Q000187:drug effects / Q000502:physiology; D036563:Cyclic ADP-Ribose / Q000378:metabolism* / Q000494:pharmacology; D003593:Cytoplasm / Q000187:drug effects / Q000502:physiology; D004338:Drug Combinations; D004553:Electric Conductivity; D006801:Humans; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism / Q000494:pharmacology; D007473:Ion Channels / Q000502:physiology; D008562:Membrane Glycoproteins; D008861:Microsomes / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D020545:Respiratory Mucosa / Q000166:cytology / Q000201:enzymology*; D012433:Ryanodine / Q000494:pharmacology; D015290:Second Messenger Systems / Q000502:physiology*; D016559:Tacrolimus / Q000494:pharmacology; D014132:Trachea / Q000166:cytology / Q000201:enzymology*
D015703:Antigens, CD; D018118:Chloride Channels; D004338:Drug Combinations; D007473:Ion Channels; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D036563:Cyclic ADP-Ribose; D012433:Ryanodine; D015544:Inositol 1,4,5-Trisphosphate; D036541:ADP-ribosyl Cyclase; C498154:CD38 protein, human; D051997:ADP-ribosyl Cyclase 1; D000109:Acetylcholine; D002118:Calcium; D016559:Tacrolimus