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. 1992 Jun 15;89(12):5326–5330. doi: 10.1073/pnas.89.12.5326

Parathyroid hormone-related protein in the rat urinary bladder: a smooth muscle relaxant produced locally in response to mechanical stretch.

M Yamamoto 1, S C Harm 1, W A Grasser 1, M A Thiede 1
PMCID: PMC49284  PMID: 1376916

Abstract

Parathyroid hormone-related protein (PTHrP) gene expression in the pregnant rat uterus has been shown to be dependent on occupancy of the uterus by the fetus. To further test the hypothesis that the synthesis of PTHrP in smooth muscle tissue is regulated by mechanical stretch, we conducted experiments using the rat urinary bladder as a model of an expansible hollow organ. The results indicate that PTHrP mRNA levels do change in response to the stretch of the bladder wall. Under normal conditions PTHrP mRNA levels in the bladder correlated with the urine volume-namely, the extent of bladder distension. When bladders were maintained empty in vivo, PTHrP mRNA levels decreased gradually. Conversely, when bladders were distended by the accumulation of urine, levels of PTHrP mRNA increased dramatically with time. When distension was limited to one-half of the bladder, the increase in PTHrP mRNA was observed only in the distended portion. Histochemical studies performed on distended bladder tissue indicated the presence of PTHrP immunoreactivity in smooth muscle cells. Isolated organ bath studies were used to examine the possible physiological role of PTHrP in smooth muscle tonicity. In vitro responsiveness of bladder muscle strips to exogenous PTHrP was dependent on the in vivo condition of the bladder. In muscle strips obtained from bladders kept empty in vivo, PTHrP-(1-34)-NH2 relaxed carbachol-induced contraction in a dose-dependent manner but failed to relax the contraction in muscle strips from distended bladders that had high endogenous PTHrP expression. These results and the previous findings in the rat uterus suggest a physiological role of PTHrP in bladder smooth muscle 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. Andersson P. O., Bloom S. R., Mattiasson A., Uvelius B. Changes in vascular resistance in the feline urinary bladder in response to bladder filling. J Urol. 1985 Nov;134(5):1041–1046. doi: 10.1016/s0022-5347(17)47584-7. [DOI] [PubMed] [Google Scholar]
  2. Broadus A. E., Mangin M., Ikeda K., Insogna K. L., Weir E. C., Burtis W. J., Stewart A. F. Humoral hypercalcemia of cancer. Identification of a novel parathyroid hormone-like peptide. N Engl J Med. 1988 Sep 1;319(9):556–563. doi: 10.1056/NEJM198809013190906. [DOI] [PubMed] [Google Scholar]
  3. Chorev M., Goldman M. E., McKee R. L., Roubini E., Levy J. J., Gay C. T., Reagan J. E., Fisher J. E., Caporale L. H., Golub E. E. Modifications of position 12 in parathyroid hormone and parathyroid hormone related protein: toward the design of highly potent antagonists. Biochemistry. 1990 Feb 13;29(6):1580–1586. doi: 10.1021/bi00458a032. [DOI] [PubMed] [Google Scholar]
  4. Drucker D. J., Asa S. L., Henderson J., Goltzman D. The parathyroid hormone-like peptide gene is expressed in the normal and neoplastic human endocrine pancreas. Mol Endocrinol. 1989 Oct;3(10):1589–1595. doi: 10.1210/mend-3-10-1589. [DOI] [PubMed] [Google Scholar]
  5. Gu J., D'Andrea M., Seethapathy M. Atrial natriuretic peptide and its messenger ribonucleic acid in overloaded and overload-released ventricles of rat. Endocrinology. 1989 Oct;125(4):2066–2074. doi: 10.1210/endo-125-4-2066. [DOI] [PubMed] [Google Scholar]
  6. Horiuchi N., Caulfield M. P., Fisher J. E., Goldman M. E., McKee R. L., Reagan J. E., Levy J. J., Nutt R. F., Rodan S. B., Schofield T. L. Similarity of synthetic peptide from human tumor to parathyroid hormone in vivo and in vitro. Science. 1987 Dec 11;238(4833):1566–1568. doi: 10.1126/science.3685994. [DOI] [PubMed] [Google Scholar]
  7. Ikeda K., Weir E. C., Mangin M., Dannies P. S., Kinder B., Deftos L. J., Brown E. M., Broadus A. E. Expression of messenger ribonucleic acids encoding a parathyroid hormone-like peptide in normal human and animal tissues with abnormal expression in human parathyroid adenomas. Mol Endocrinol. 1988 Dec;2(12):1230–1236. doi: 10.1210/mend-2-12-1230. [DOI] [PubMed] [Google Scholar]
  8. Kemp B. E., Moseley J. M., Rodda C. P., Ebeling P. R., Wettenhall R. E., Stapleton D., Diefenbach-Jagger H., Ure F., Michelangeli V. P., Simmons H. A. Parathyroid hormone-related protein of malignancy: active synthetic fragments. Science. 1987 Dec 11;238(4833):1568–1570. doi: 10.1126/science.3685995. [DOI] [PubMed] [Google Scholar]
  9. Komuro I., Kaida T., Shibazaki Y., Kurabayashi M., Katoh Y., Hoh E., Takaku F., Yazaki Y. Stretching cardiac myocytes stimulates protooncogene expression. J Biol Chem. 1990 Mar 5;265(7):3595–3598. [PubMed] [Google Scholar]
  10. Kramer S., Reynolds F. H., Jr, Castillo M., Valenzuela D. M., Thorikay M., Sorvillo J. M. Immunological identification and distribution of parathyroid hormone-like protein polypeptides in normal and malignant tissues. Endocrinology. 1991 Apr;128(4):1927–1937. doi: 10.1210/endo-128-4-1927. [DOI] [PubMed] [Google Scholar]
  11. Lansman J. B., Hallam T. J., Rink T. J. Single stretch-activated ion channels in vascular endothelial cells as mechanotransducers? 1987 Feb 26-Mar 4Nature. 325(6107):811–813. doi: 10.1038/325811a0. [DOI] [PubMed] [Google Scholar]
  12. Mangin M., Ikeda K., Broadus A. E. Structure of the mouse gene encoding parathyroid hormone-related peptide. Gene. 1990 Nov 15;95(2):195–202. doi: 10.1016/0378-1119(90)90362-u. [DOI] [PubMed] [Google Scholar]
  13. Mangin M., Webb A. C., Dreyer B. E., Posillico J. T., Ikeda K., Weir E. C., Stewart A. F., Bander N. H., Milstone L., Barton D. E. Identification of a cDNA encoding a parathyroid hormone-like peptide from a human tumor associated with humoral hypercalcemia of malignancy. Proc Natl Acad Sci U S A. 1988 Jan;85(2):597–601. doi: 10.1073/pnas.85.2.597. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Martin T. J., Suva L. J. Parathyroid hormone-related protein in hypercalcaemia of malignancy. Clin Endocrinol (Oxf) 1989 Nov;31(5):631–647. doi: 10.1111/j.1365-2265.1989.tb01288.x. [DOI] [PubMed] [Google Scholar]
  15. Mok L. L., Ajiwe E., Martin T. J., Thompson J. C., Cooper C. W. Parathyroid hormone-related protein relaxes rat gastric smooth muscle and shows cross-desensitization with parathyroid hormone. J Bone Miner Res. 1989 Jun;4(3):433–439. doi: 10.1002/jbmr.5650040319. [DOI] [PubMed] [Google Scholar]
  16. Nickols G. A., Nana A. D., Nickols M. A., DiPette D. J., Asimakis G. K. Hypotension and cardiac stimulation due to the parathyroid hormone-related protein, humoral hypercalcemia of malignancy factor. Endocrinology. 1989 Aug;125(2):834–841. doi: 10.1210/endo-125-2-834. [DOI] [PubMed] [Google Scholar]
  17. Nickols G. A., Nickols M. A., Helwig J. J. Binding of parathyroid hormone and parathyroid hormone-related protein to vascular smooth muscle of rabbit renal microvessels. Endocrinology. 1990 Feb;126(2):721–727. doi: 10.1210/endo-126-2-721. [DOI] [PubMed] [Google Scholar]
  18. Orloff J. J., Wu T. L., Stewart A. F. Parathyroid hormone-like proteins: biochemical responses and receptor interactions. Endocr Rev. 1989 Nov;10(4):476–495. doi: 10.1210/edrv-10-4-476. [DOI] [PubMed] [Google Scholar]
  19. Schermer D. T., Chan S. D., Bruce R., Nissenson R. A., Wood W. I., Strewler G. J. Chicken parathyroid hormone-related protein and its expression during embryologic development. J Bone Miner Res. 1991 Feb;6(2):149–155. doi: 10.1002/jbmr.5650060208. [DOI] [PubMed] [Google Scholar]
  20. Selvanayagam P., Graves K., Cooper C., Rajaraman S. Expression of the parathyroid hormone-related peptide gene in rat tissues. Lab Invest. 1991 May;64(5):713–717. [PubMed] [Google Scholar]
  21. Shew R. L., Yee J. A., Kliewer D. B., Keflemariam Y. J., McNeill D. L. Parathyroid hormone-related protein inhibits stimulated uterine contraction in vitro. J Bone Miner Res. 1991 Sep;6(9):955–959. doi: 10.1002/jbmr.5650060909. [DOI] [PubMed] [Google Scholar]
  22. Suva L. J., Winslow G. A., Wettenhall R. E., Hammonds R. G., Moseley J. M., Diefenbach-Jagger H., Rodda C. P., Kemp B. E., Rodriguez H., Chen E. Y. A parathyroid hormone-related protein implicated in malignant hypercalcemia: cloning and expression. Science. 1987 Aug 21;237(4817):893–896. doi: 10.1126/science.3616618. [DOI] [PubMed] [Google Scholar]
  23. Thiede M. A., Daifotis A. G., Weir E. C., Brines M. L., Burtis W. J., Ikeda K., Dreyer B. E., Garfield R. E., Broadus A. E. Intrauterine occupancy controls expression of the parathyroid hormone-related peptide gene in preterm rat myometrium. Proc Natl Acad Sci U S A. 1990 Sep;87(18):6969–6973. doi: 10.1073/pnas.87.18.6969. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Thiede M. A., Harm S. C., McKee R. L., Grasser W. A., Duong L. T., Leach R. M., Jr Expression of the parathyroid hormone-related protein gene in the avian oviduct: potential role as a local modulator of vascular smooth muscle tension and shell gland motility during the egg-laying cycle. Endocrinology. 1991 Oct;129(4):1958–1966. doi: 10.1210/endo-129-4-1958. [DOI] [PubMed] [Google Scholar]
  25. Thiede M. A., Rodan G. A. Expression of a calcium-mobilizing parathyroid hormone-like peptide in lactating mammary tissue. Science. 1988 Oct 14;242(4876):278–280. doi: 10.1126/science.3175653. [DOI] [PubMed] [Google Scholar]
  26. Thiede M. A., Strewler G. J., Nissenson R. A., Rosenblatt M., Rodan G. A. Human renal carcinoma expresses two messages encoding a parathyroid hormone-like peptide: evidence for the alternative splicing of a single-copy gene. Proc Natl Acad Sci U S A. 1988 Jul;85(13):4605–4609. doi: 10.1073/pnas.85.13.4605. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Thompson D. D., Seedor J. G., Fisher J. E., Rosenblatt M., Rodan G. A. Direct action of the parathyroid hormone-like human hypercalcemic factor on bone. Proc Natl Acad Sci U S A. 1988 Aug;85(15):5673–5677. doi: 10.1073/pnas.85.15.5673. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Weir E. C., Brines M. L., Ikeda K., Burtis W. J., Broadus A. E., Robbins R. J. Parathyroid hormone-related peptide gene is expressed in the mammalian central nervous system. Proc Natl Acad Sci U S A. 1990 Jan;87(1):108–112. doi: 10.1073/pnas.87.1.108. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Winquist R. J., Baskin E. P., Vlasuk G. P. Synthetic tumor-derived human hypercalcemic factor exhibits parathyroid hormone-like vasorelaxation in renal arteries. Biochem Biophys Res Commun. 1987 Nov 30;149(1):227–232. doi: 10.1016/0006-291x(87)91628-7. [DOI] [PubMed] [Google Scholar]
  30. Yamamoto M., Duong L. T., Fisher J. E., Thiede M. A., Caulfield M. P., Rosenblatt M. Suckling-mediated increases in urinary phosphate and 3',5'-cyclic adenosine monophosphate excretion in lactating rats: possible systemic effects of parathyroid hormone-related protein. Endocrinology. 1991 Nov;129(5):2614–2622. doi: 10.1210/endo-129-5-2614. [DOI] [PubMed] [Google Scholar]
  31. Yasuda T., Banville D., Rabbani S. A., Hendy G. N., Goltzman D. Rat parathyroid hormone-like peptide: comparison with the human homologue and expression in malignant and normal tissue. Mol Endocrinol. 1989 Mar;3(3):518–525. doi: 10.1210/mend-3-3-518. [DOI] [PubMed] [Google Scholar]

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