Protein kinase C blocks somatostatin-induced modulation of calcium current in chick sympathetic neurons.
1. Somatostatin produces a voltage-dependent inhibition of N-type Ca2+ current in chick sympathetic neurons. Pretreatment of chick sympathetic ganglion neurons with protein kinase C (PKC) activators has no effect on calcium current (ICa) but reduces the inhibition of ICa by somatostatin. 2. The effects of the alkaloid PKC activator (-)-indolactam V were indistinguishable from those of 4 beta-phorbol-12-myristate-13-acetate (4 beta-PMA). The inactive isomers (+)-indolactam V and 4 alpha-PMA did not alter the modulation of ICa by somatostatin. 3. Modulation of ICa by somatostatin desensitizes, with a time for half desensitization of approximately 3 min. PKC activation mimics the normal desensitization process in that responses to 30 nM somatostatin are inhibited to a greater extent than are responses to 1 microM somatostatin. 4. PKC appears to act at the level of the somatostatin receptor or receptor-G protein interaction because PKC activation does not alter Ca2+ current inhibition in response to a nonhydrolyzable analog of GTP, GTP-gamma-S, which directly activates G proteins. 5. The specific PKC inhibitor calphostin C largely reverses the effects of phorbol esters, but does not slow the normal rate of desensitization of somatostatin responses. This indicates that PKC is not involved in the homologous desensitization of the somatostatin receptor. 6. Neither substance P, which activates PKC in these cells, nor arachidonic acid, another PKC activator, altered the action of somatostatin on ICa.
Golard
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A
Department of Cell Biology, Columbia University, New York 10032.
Role
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LW
Siegelbaum
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D000818:Animals; D015220:Calcium Channels / Q000187:drug effects*; D002642:Chick Embryo; D004558:Electric Stimulation; D004789:Enzyme Activation / Q000187:drug effects; D019204:GTP-Binding Proteins / Q000378:metabolism; D005728:Ganglia, Sympathetic / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology; D007769:Lactams / Q000494:pharmacology; D009281:Naphthalenes; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D011083:Polycyclic Compounds / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D017481:Receptors, Somatostatin / Q000187:drug effects; D013004:Somatostatin / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D013564:Sympathetic Nervous System / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D015220:Calcium Channels; D007211:Indoles; D007769:Lactams; D009281:Naphthalenes; D011083:Polycyclic Compounds; D017481:Receptors, Somatostatin; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D013004:Somatostatin; C043969:indolactam V; D011493:Protein Kinase C; D019204:GTP-Binding Proteins; C058819:calphostin C; D013755:Tetradecanoylphorbol Acetate