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. 1995 May 23;92(11):5052–5056. doi: 10.1073/pnas.92.11.5052

Neurosecretory habituation in PC12 cells: modulation during parallel habituation.

P T Martin 1, D E Koshland Jr 1
PMCID: PMC41846  PMID: 7761447

Abstract

PC12 cells habituate during repetitive stimulation with acetylcholine, bradykinin, or high potassium. Interspersing these stimulants did not affect the rate of habituation of the others, but it could modulate the amplitude of the norepinephrine secretion each could achieve. Stimulation with acetylcholine inhibited norepinephrine secretion caused by high potassium and bradykinin stimulation, while high potassium had no effect on acetylcholine or bradykinin, and bradykinin increased secretion caused by acetylcholine. Changes in norepinephrine secretion resulting from any of these stimulants correlated with changes in internal calcium levels. Cyclic AMP-, protein kinase C-, and calmodulin-dependent second messenger pathways all modulated norepinephrine secretion caused by acetylcholine and high potassium and showed a distinct hierarchy in their effectiveness. These data demonstrate that different receptor pathways can change the norepinephrine response of one another while not changing the levels of the molecules responsible for habituation.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Cheever L., Koshland D. E., Jr Retention of habituation in PC12 cells. Proc Natl Acad Sci U S A. 1992 Nov 1;89(21):10084–10088. doi: 10.1073/pnas.89.21.10084. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Di Virgilio F., Milani D., Leon A., Meldolesi J., Pozzan T. Voltage-dependent activation and inactivation of calcium channels in PC12 cells. Correlation with neurotransmitter release. J Biol Chem. 1987 Jul 5;262(19):9189–9195. [PubMed] [Google Scholar]
  3. Dichter M. A., Tischler A. S., Greene L. A. Nerve growth factor-induced increase in electrical excitability and acetylcholine sensitivity of a rat pheochromocytoma cell line. Nature. 1977 Aug 11;268(5620):501–504. doi: 10.1038/268501a0. [DOI] [PubMed] [Google Scholar]
  4. Fasolato C., Pandiella A., Meldolesi J., Pozzan T. Generation of inositol phosphates, cytosolic Ca2+, and ionic fluxes in PC12 cells treated with bradykinin. J Biol Chem. 1988 Nov 25;263(33):17350–17359. [PubMed] [Google Scholar]
  5. Greene L. A., Rein G. Release, storage and uptake of catecholamines by a clonal cell line of nerve growth factor (NGF) responsive pheo-chromocytoma cells. Brain Res. 1977 Jul 1;129(2):247–263. doi: 10.1016/0006-8993(77)90005-1. [DOI] [PubMed] [Google Scholar]
  6. Greene L. A., Tischler A. S. Establishment of a noradrenergic clonal line of rat adrenal pheochromocytoma cells which respond to nerve growth factor. Proc Natl Acad Sci U S A. 1976 Jul;73(7):2424–2428. doi: 10.1073/pnas.73.7.2424. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Guroff G., Dickens G., End D., Londos C. The action of adenosine analogs on PC12 cells. J Neurochem. 1981 Dec;37(6):1431–1439. doi: 10.1111/j.1471-4159.1981.tb06312.x. [DOI] [PubMed] [Google Scholar]
  8. Kandel E. R., Schwartz J. H. Molecular biology of learning: modulation of transmitter release. Science. 1982 Oct 29;218(4571):433–443. doi: 10.1126/science.6289442. [DOI] [PubMed] [Google Scholar]
  9. Martin P. T., Chung B. T., Koshland D. E., Jr Regulation of neurosecretory habituation by cAMP. Role of adaptation of cAMP signals. Eur J Biochem. 1993 Oct 1;217(1):259–265. doi: 10.1111/j.1432-1033.1993.tb18241.x. [DOI] [PubMed] [Google Scholar]
  10. Martin P. T., Koshland D. E., Jr Regulation of neurosecretory habituation in PC12 cells: parallel pathways used by cAMP and calcium. Proc Natl Acad Sci U S A. 1992 Nov 1;89(21):10257–10261. doi: 10.1073/pnas.89.21.10257. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Martin P. T., Koshland D. E., Jr The biochemistry of the neuron. Neurosecretory habituation to repetitive depolarizations in PC12 cells. J Biol Chem. 1991 Apr 25;266(12):7388–7392. [PubMed] [Google Scholar]
  12. McFadden P. N., Koshland D. E., Jr Habituation in the single cell: diminished secretion of norepinephrine with repetitive depolarization of PC12 cells. Proc Natl Acad Sci U S A. 1990 Mar;87(5):2031–2035. doi: 10.1073/pnas.87.5.2031. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Meldolesi J., Huttner W. B., Tsien R. Y., Pozzan T. Free cytoplasmic Ca2+ and neurotransmitter release: studies on PC12 cells and synaptosomes exposed to alpha-latrotoxin. Proc Natl Acad Sci U S A. 1984 Jan;81(2):620–624. doi: 10.1073/pnas.81.2.620. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Mills J. S., Bailey B. L., Johnson J. D. Cooperativity among calmodulin's drug binding sites. Biochemistry. 1985 Aug 27;24(18):4897–4902. doi: 10.1021/bi00339a026. [DOI] [PubMed] [Google Scholar]
  15. Newton A. C., Koshland D. E., Jr High cooperativity, specificity, and multiplicity in the protein kinase C-lipid interaction. J Biol Chem. 1989 Sep 5;264(25):14909–14915. [PubMed] [Google Scholar]
  16. Nishizuka Y. Studies and perspectives of protein kinase C. Science. 1986 Jul 18;233(4761):305–312. doi: 10.1126/science.3014651. [DOI] [PubMed] [Google Scholar]
  17. Pozzan T., Gatti G., Dozio N., Vicentini L. M., Meldolesi J. Ca2+-dependent and -independent release of neurotransmitters from PC12 cells: a role for protein kinase C activation? J Cell Biol. 1984 Aug;99(2):628–638. doi: 10.1083/jcb.99.2.628. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Thompson R. F., Spencer W. A. Habituation: a model phenomenon for the study of neuronal substrates of behavior. Psychol Rev. 1966 Jan;73(1):16–43. doi: 10.1037/h0022681. [DOI] [PubMed] [Google Scholar]
  19. Vicentini L. M., Di Virgilio F., Ambrosini A., Pozzan T., Meldolesi J. Tumor promoter phorbol 12-myristate, 13-acetate inhibits phosphoinositide hydrolysis and cytosolic Ca2+ rise induced by the activation of muscarinic receptors in PC12 cells. Biochem Biophys Res Commun. 1985 Feb 28;127(1):310–317. doi: 10.1016/s0006-291x(85)80160-1. [DOI] [PubMed] [Google Scholar]

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