Ca2+ mobilized by caffeine from the inositol 1,4,5-trisphosphate-insensitive pool of Ca2+ in somatic regions of sympathetic neurons does not evoke [3H]norepinephrine release.
The effects of electrical stimulation, muscarinic and serotonergic agonists, and caffeine on [3H]inositol 1,4,5-trisphosphate ([3H]Ins(1,4,5)P3) content, intracellular free Ca2+ concentration ([Ca2+]i), and release of [3H]norepinephrine ([3H]NE) were studied in cultured sympathetic neurons. Neuronal cell body [Ca2+]i was unaffected by muscarinic or serotonergic receptor stimulation, which significantly increased [3H]Ins(1,4,5)P3 content. Stimulation at 2 Hz and caffeine had no effect on [3H]Ins(1,4,5)P3, but caused greater than two-fold increase in [Ca2+]i. Only 2-Hz stimulation released [3H]NE. Caffeine had no effect on the release. When [Ca2+]i was measured in growth cones, only electrical stimulation produced an increase in [Ca2+]i. The other agents had no effect on Ca2+ at the terminal regions of the neurons. We conclude that Ins(1,4,5)P3-insensitive, but caffeine-sensitive Ca2+ stores in sympathetic neurons are located only in the cell body and are not coupled to [3H]NE release.
Department of Pharmacology, Wayne State University School of Medicine, Detroit, MI 48201.
T D
TD
Wakade
S V
SV
Bhave
A
A
Bhave
D A
DA
Przywara
A R
AR
Wakade
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D002110:Caffeine / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D004558:Electric Stimulation; D015544:Inositol 1,4,5-Trisphosphate / Q000494:pharmacology*; D009474:Neurons / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism*; D009994:Osmolar Concentration; D012701:Serotonin / Q000494:pharmacology; D013564:Sympathetic Nervous System / Q000166:cytology / Q000378:metabolism*; D014316:Tritium
D014316:Tritium; D012701:Serotonin; D002110:Caffeine; D015544:Inositol 1,4,5-Trisphosphate; D000109:Acetylcholine; D002118:Calcium; D009638:Norepinephrine