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. 1995 May 23;92(11):5219–5223. doi: 10.1073/pnas.92.11.5219

Evidence for a role of pituitary ATP receptors in the regulation of pituitary function.

Z P Chen 1, M Kratzmeier 1, A Levy 1, C A McArdle 1, A Poch 1, A Day 1, A K Mukhopadhyay 1, S L Lightman 1
PMCID: PMC41880  PMID: 7761477

Abstract

Despite a rapidly increasing acceptance for a role of ATP as an extracellular mediator in several biological systems, the present report shows that ATP may mediate physiological responses in pituitary cells. We have now been able to demonstrate a specific action of ATP receptors to mediate the release of luteinizing hormone from gonadotropes and have coupled them with further studies that clearly show that ATP can be exocytotically released from cultured rat pituitary cells. Both ATP and UTP (100 microM) caused a > 14-fold increase in the rate of luteinizing hormone release from superfused cells. Adenosine 5'-[alpha, beta-methylene]triphosphate and 5'-[beta,gamma-methylene triphosphate were ineffective, and 2-methylthio-ATP had only a modest stimulatory effect. Homologous and heterologous desensitization occurred with UTP and ATP, and these did not have additive effects. Thus, nucleotides can be effective stimulators of luteinizing hormone release through a single class of ATP receptor (P2U subtype). The calcium ionophore A23187 provoked release of a substantial amount of ATP from pituitary cells in a concentration- and Ca(2+)-dependent manner, which was desensitized by pretreatment with A23187. This implies a possible paracrine and/or autocrine mechanism by which nucleotides may exert their effects on pituitary cells. In conclusion, we have provided strong evidence for a novel role of extracellular nucleotides as mediators in pituitary--in particular, in gonadotrope--function.

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Selected References

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

  1. Abbracchio M. P., Burnstock G. Purinoceptors: are there families of P2X and P2Y purinoceptors? Pharmacol Ther. 1994;64(3):445–475. doi: 10.1016/0163-7258(94)00048-4. [DOI] [PubMed] [Google Scholar]
  2. BORN G. V. Changes in the distribution of phosphorus in platelet-rich plasma during clotting. Biochem J. 1958 Apr;68(4):695–704. doi: 10.1042/bj0680695. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bean B. P. Pharmacology and electrophysiology of ATP-activated ion channels. Trends Pharmacol Sci. 1992 Mar;13(3):87–90. doi: 10.1016/0165-6147(92)90032-2. [DOI] [PubMed] [Google Scholar]
  4. Brake A. J., Wagenbach M. J., Julius D. New structural motif for ligand-gated ion channels defined by an ionotropic ATP receptor. Nature. 1994 Oct 6;371(6497):519–523. doi: 10.1038/371519a0. [DOI] [PubMed] [Google Scholar]
  5. Burnstock G., Kennedy C. Is there a basis for distinguishing two types of P2-purinoceptor? Gen Pharmacol. 1985;16(5):433–440. doi: 10.1016/0306-3623(85)90001-1. [DOI] [PubMed] [Google Scholar]
  6. Chen Z. P., Levy A., Lightman S. L. Activation of specific ATP receptors induces a rapid increase in intracellular calcium ions in rat hypothalamic neurons. Brain Res. 1994 Apr 4;641(2):249–256. doi: 10.1016/0006-8993(94)90151-1. [DOI] [PubMed] [Google Scholar]
  7. Chen Z. P., Levy A., McArdle C. A., Lightman S. L. Pituitary ATP receptors: characterization and functional localization to gonadotropes. Endocrinology. 1994 Sep;135(3):1280–1283. doi: 10.1210/endo.135.3.8070374. [DOI] [PubMed] [Google Scholar]
  8. Davidson J. S., Wakefield I. K., Sohnius U., van der Merwe P. A., Millar R. P. A novel extracellular nucleotide receptor coupled to phosphoinositidase-C in pituitary cells. Endocrinology. 1990 Jan;126(1):80–87. doi: 10.1210/endo-126-1-80. [DOI] [PubMed] [Google Scholar]
  9. Deber C. M., Tom-Kun J., Mack E., Grinstein S. Bromo-A23187: a nonfluorescent calcium ionophore for use with fluorescent probes. Anal Biochem. 1985 May 1;146(2):349–352. doi: 10.1016/0003-2697(85)90550-0. [DOI] [PubMed] [Google Scholar]
  10. Douglas W. W., Poisner A. M. Evidence that the secreting adrenal chromaffin cell releases catecholamines directly from ATP-rich granules. J Physiol. 1966 Mar;183(1):236–248. doi: 10.1113/jphysiol.1966.sp007863. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Dubyak G. R. Signal transduction by P2-purinergic receptors for extracellular ATP. Am J Respir Cell Mol Biol. 1991 Apr;4(4):295–300. doi: 10.1165/ajrcmb/4.4.295. [DOI] [PubMed] [Google Scholar]
  12. Edwards F. A., Gibb A. J., Colquhoun D. ATP receptor-mediated synaptic currents in the central nervous system. Nature. 1992 Sep 10;359(6391):144–147. doi: 10.1038/359144a0. [DOI] [PubMed] [Google Scholar]
  13. Fredholm B. B., Abbracchio M. P., Burnstock G., Daly J. W., Harden T. K., Jacobson K. A., Leff P., Williams M. Nomenclature and classification of purinoceptors. Pharmacol Rev. 1994 Jun;46(2):143–156. [PMC free article] [PubMed] [Google Scholar]
  14. Fried G. Small noradrenergic storage vesicles isolated from rat vas deferens--biochemical and morphological characterization. Acta Physiol Scand Suppl. 1980;493:1–28. [PubMed] [Google Scholar]
  15. Gordon J. L. Extracellular ATP: effects, sources and fate. Biochem J. 1986 Jan 15;233(2):309–319. doi: 10.1042/bj2330309. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Huckle W. R., Conn P. M. Molecular mechanism of gonadotropin releasing hormone action. II. The effector system. Endocr Rev. 1988 Nov;9(4):387–395. doi: 10.1210/edrv-9-4-387. [DOI] [PubMed] [Google Scholar]
  17. Kastritsis C. H., Salm A. K., McCarthy K. Stimulation of the P2Y purinergic receptor on type 1 astroglia results in inositol phosphate formation and calcium mobilization. J Neurochem. 1992 Apr;58(4):1277–1284. doi: 10.1111/j.1471-4159.1992.tb11339.x. [DOI] [PubMed] [Google Scholar]
  18. Lustig K. D., Shiau A. K., Brake A. J., Julius D. Expression cloning of an ATP receptor from mouse neuroblastoma cells. Proc Natl Acad Sci U S A. 1993 Jun 1;90(11):5113–5117. doi: 10.1073/pnas.90.11.5113. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. McArdle C. A., Poch A. Dependence of gonadotropin-releasing hormone-stimulated luteinizing hormone release upon intracellular Ca2+ pools is revealed by desensitization and thapsigargin blockade. Endocrinology. 1992 Jun;130(6):3567–3574. doi: 10.1210/endo.130.6.1534542. [DOI] [PubMed] [Google Scholar]
  20. Osipchuk Y., Cahalan M. Cell-to-cell spread of calcium signals mediated by ATP receptors in mast cells. Nature. 1992 Sep 17;359(6392):241–244. doi: 10.1038/359241a0. [DOI] [PubMed] [Google Scholar]
  21. Rojas E., Pollard H. B., Heldman E. Real-time measurements of acetylcholine-induced release of ATP from bovine medullary chromaffin cells. FEBS Lett. 1985 Jun 17;185(2):323–327. doi: 10.1016/0014-5793(85)80931-5. [DOI] [PubMed] [Google Scholar]
  22. Sussman K. E., Leitner J. W. Conversion of ATP into other adenine nucleotides within isolated islet secretory vesicles. Effect of cyclic AMP on phosphorus translocation. Endocrinology. 1977 Sep;101(3):694–701. doi: 10.1210/endo-101-3-694. [DOI] [PubMed] [Google Scholar]
  23. Valera S., Hussy N., Evans R. J., Adami N., North R. A., Surprenant A., Buell G. A new class of ligand-gated ion channel defined by P2x receptor for extracellular ATP. Nature. 1994 Oct 6;371(6497):516–519. doi: 10.1038/371516a0. [DOI] [PubMed] [Google Scholar]
  24. Volknandt W., Zimmermann H. Acetylcholine, ATP, and proteoglycan are common to synaptic vesicles isolated from the electric organs of electric eel and electric catfish as well as from rat diaphragm. J Neurochem. 1986 Nov;47(5):1449–1462. doi: 10.1111/j.1471-4159.1986.tb00778.x. [DOI] [PubMed] [Google Scholar]
  25. Webb T. E., Simon J., Krishek B. J., Bateson A. N., Smart T. G., King B. F., Burnstock G., Barnard E. A. Cloning and functional expression of a brain G-protein-coupled ATP receptor. FEBS Lett. 1993 Jun 14;324(2):219–225. doi: 10.1016/0014-5793(93)81397-i. [DOI] [PubMed] [Google Scholar]
  26. White T. D. Direct detection of depolarisation-induced release of ATP from a synaptosomal preparation. Nature. 1977 May 5;267(5606):67–68. doi: 10.1038/267067a0. [DOI] [PubMed] [Google Scholar]
  27. White T. D. Release of ATP from a synaptosomal preparation by elevated extracellular K+ and by veratridine. J Neurochem. 1978 Feb;30(2):329–336. doi: 10.1111/j.1471-4159.1978.tb06534.x. [DOI] [PubMed] [Google Scholar]

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