Functional relation between caffeine- and muscarine-sensitive Ca2+ stores and no Ca2+ releasing action of cyclic adenosine diphosphate-ribose in guinea-pig adrenal chromaffin cells.
In voltage-clamped guinea-pig chromaffin cells, muscarine (50 microM) or caffeine (30 mM) produced a transient intracellular Ca(2+) concentration ([Ca(2+)](i)) increase, catecholamine release and an outward K(+) current mediated through Ca(2+) released from internal Ca(2+) stores at a holding potential of -40 mV. Caffeine followed by muscarine failed to evoke these responses, while muscarine followed by caffeine was effective in producing about 30% of [Ca(2+)](i) increase and catecholamine secretion. In cells dialyzed with inositol 1,4,5-trisphosphate (IP(3)), caffeine failed to produce the [Ca(2+)](i) increase. Intracellular application of cyclic adenosine 5'-diphosphate-ribose (cADP-ribose) or 8-bromo cADP-ribose exerted no effect on the resting [Ca(2+)](i) and the caffeine-induced [Ca(2+)](i) increase. These results suggest that IP(3)-sensitive stores are functionally divided into two subpopulations, sensitive and insensitive to caffeine, and it is unlikely that cADP-ribose plays a role as a Ca(2+) releaser in guinea-pig adrenal chromaffin cells.
Ohta
Toshio
T
Laboratory of Pharmacology, Department of Biomedical Science, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo 060-0818, Japan. tohta@vetmed.hokudai.ac.jp
Wakade
Arun R
AR
Yonekubo
Kazuki
K
Ito
Shigeo
S
D000311:Adrenal Glands / Q000187:drug effects / Q000502:physiology; D000818:Animals; D002110:Caffeine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D000697:Central Nervous System Stimulants / Q000494:pharmacology; D019439:Chromaffin Cells / Q000187:drug effects / Q000378:metabolism*; D036563:Cyclic ADP-Ribose / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology; D003956:Dialysis; D006168:Guinea Pigs; D015544:Inositol 1,4,5-Trisphosphate / Q000008:administration & dosage / Q000494:pharmacology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009116:Muscarine / Q000494:pharmacology; D018721:Muscarinic Agonists / Q000494:pharmacology; D018408:Patch-Clamp Techniques
D000697:Central Nervous System Stimulants; D018721:Muscarinic Agonists; D036563:Cyclic ADP-Ribose; D002110:Caffeine; D009116:Muscarine; D015544:Inositol 1,4,5-Trisphosphate; D002118:Calcium