Skip to main content
British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 1990 Oct;101(2):411–417. doi: 10.1111/j.1476-5381.1990.tb12723.x

Inhibitory effect of streptozotocin-induced diabetes on non-cholinergic motor transmission in rat detrusor and its prevention by sorbinil.

G N Luheshi 1, M A Zar 1
PMCID: PMC1917679  PMID: 2175235

Abstract

1. Non-cholinergic motor transmission in the urinary bladder of streptozotocin (STZ)-diabetic rats was studied by recording contractile activity of strips of detrusor in vitro. 2. The neurogenic contractile responses to electrical field stimulation (EFS) of atropine-treated detrusor strips were decreased in 4, 8 and 12 week STZ-diabetic rats. The decrease was most marked in 12 week diabetic rats and least in 4 week ones. 3. Concentration-response curves showed no change in sensitivity of the detrusor to acetylcholine (ACh) in diabetic rats. The maximum tension generated by ACh was similar in diabetic and non-diabetic animals. 4. The contractile responses to EFS at frequencies greater than or equal to 1 Hz were not maintained during stimulation. The 'fade' was significantly greater in detrusor strips of diabetic rats. 5. The contractile response of detrusor to EFS was significantly greater in 12 week diabetic rats treated with the aldose reductase inhibitor sorbinil, than in untreated 12 week diabetic rats. The sensitivity to ACh was similar in the two groups. 6. It is concluded that the reduction of the neurogenic non-cholinergic responses of detrusor to EFS in STZ-diabetic rats is probably caused by a reduction in the release of the non-cholinergic motor transmitter. The results are discussed in relation to bladder dysfunction in human diabetes mellitus.

Full text

PDF
412

Selected References

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

  1. Ambache N., Zar M. A. Non-cholinergic transmission by post-ganglionic motor neurones in the mammalian bladder. J Physiol. 1970 Oct;210(3):761–783. doi: 10.1113/jphysiol.1970.sp009240. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Buck A. C., McRae C. U., Chisholm G. D. The diabetic bladder. Proc R Soc Med. 1974 Jan;67(1):81–83. [PMC free article] [PubMed] [Google Scholar]
  3. Burnstock G., Cocks T., Crowe R., Kasakov L. Purinergic innervation of the guinea-pig urinary bladder. Br J Pharmacol. 1978 May;63(1):125–138. doi: 10.1111/j.1476-5381.1978.tb07782.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Burnstock G., Dumsday B., Smythe A. Atropine resistant excitation of the urinary bladder: the possibility of transmission via nerves releasing a purine nucleotide. Br J Pharmacol. 1972 Mar;44(3):451–461. doi: 10.1111/j.1476-5381.1972.tb07283.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Clements R. S., Jr Diabetic neuropathy--new concepts of its etiology. Diabetes. 1979 Jun;28(6):604–611. doi: 10.2337/diab.28.6.604. [DOI] [PubMed] [Google Scholar]
  6. Downie J. W., Dean D. M. The contribution of cholinergic postganglionic neurotransmission to contractions of rabbit detrusor. J Pharmacol Exp Ther. 1977 Nov;203(2):417–425. [PubMed] [Google Scholar]
  7. Ellenberg M. Development of urinary bladder dysfunction in diabetes mellitus. Ann Intern Med. 1980 Feb;92(2 Pt 2):321–323. doi: 10.7326/0003-4819-92-2-321. [DOI] [PubMed] [Google Scholar]
  8. Faerman I., Maler M., Jadzinsky M., Alvarez E., Fox D., Zilbervarg J., Cibeira J. B., Colinas R. Asymptomatic neurogenic bladder in juvenile diabetics. Diabetologia. 1971 Jun;7(3):168–172. doi: 10.1007/BF01212549. [DOI] [PubMed] [Google Scholar]
  9. Frimodt-Møller C. Diabetic cystopathy: epidemiology and related disorders. Ann Intern Med. 1980 Feb;92(2 Pt 2):318–321. doi: 10.7326/0003-4819-92-2-318. [DOI] [PubMed] [Google Scholar]
  10. Gabbay K. H., Merola L. O., Field R. A. Sorbitol pathway: presence in nerve and cord with substrate accumulation in diabetes. Science. 1966 Jan 14;151(3707):209–210. doi: 10.1126/science.151.3707.209. [DOI] [PubMed] [Google Scholar]
  11. Gabbay K. H. The sorbitol pathway and the complications of diabetes. N Engl J Med. 1973 Apr 19;288(16):831–836. doi: 10.1056/NEJM197304192881609. [DOI] [PubMed] [Google Scholar]
  12. Greene D. A., Lattimer S., Ulbrecht J., Carroll P. Glucose-induced alterations in nerve metabolism: current perspective on the pathogenesis of diabetic neuropathy and future directions for research and therapy. Diabetes Care. 1985 May-Jun;8(3):290–299. doi: 10.2337/diacare.8.3.290. [DOI] [PubMed] [Google Scholar]
  13. Hoyle C. H., Chapple C., Burnstock G. Isolated human bladder: evidence for an adenine dinucleotide acting on P2X-purinoceptors and for purinergic transmission. Eur J Pharmacol. 1989 Dec 12;174(1):115–118. doi: 10.1016/0014-2999(89)90881-9. [DOI] [PubMed] [Google Scholar]
  14. Jaspan J., Maselli R., Herold K., Bartkus C. Treatment of severely painful diabetic neuropathy with an aldose reductase inhibitor: relief of pain and improved somatic and autonomic nerve function. Lancet. 1983 Oct 1;2(8353):758–762. doi: 10.1016/s0140-6736(83)92296-1. [DOI] [PubMed] [Google Scholar]
  15. Judzewitsch R. G., Jaspan J. B., Polonsky K. S., Weinberg C. R., Halter J. B., Halar E., Pfeifer M. A., Vukadinovic C., Bernstein L., Schneider M. Aldose reductase inhibition improves nerve conduction velocity in diabetic patients. N Engl J Med. 1983 Jan 20;308(3):119–125. doi: 10.1056/NEJM198301203080302. [DOI] [PubMed] [Google Scholar]
  16. Kinder R. B., Mundy A. R. Atropine blockade of nerve-mediated stimulation of the human detrusor. Br J Urol. 1985 Aug;57(4):418–421. doi: 10.1111/j.1464-410x.1985.tb06301.x. [DOI] [PubMed] [Google Scholar]
  17. Kolta M. G., Wallace L. J., Gerald M. C. Streptozocin-induced diabetes affects rat urinary bladder response to autonomic agents. Diabetes. 1985 Sep;34(9):917–921. doi: 10.2337/diab.34.9.917. [DOI] [PubMed] [Google Scholar]
  18. Lincoln J., Crockett M., Haven A. J., Burnstock G. Rat bladder in the early stages of streptozotocin-induced diabetes: adrenergic and cholinergic innervation. Diabetologia. 1984 Jan;26(1):81–87. doi: 10.1007/BF00252269. [DOI] [PubMed] [Google Scholar]
  19. Longhurst P. A., Belis J. A. Abnormalities of rat bladder contractility in streptozotocin-induced diabetes mellitus. J Pharmacol Exp Ther. 1986 Sep;238(3):773–777. [PubMed] [Google Scholar]
  20. Luheshi G. N., Zar M. A. Presence of non-cholinergic motor transmission in human isolated bladder. J Pharm Pharmacol. 1990 Mar;42(3):223–224. doi: 10.1111/j.2042-7158.1990.tb05396.x. [DOI] [PubMed] [Google Scholar]
  21. Mayhew J. A., Gillon K. R., Hawthorne J. N. Free and lipid inositol, sorbitol and sugars in sciatic nerve obtained post-mortem from diabetic patients and control subjects. Diabetologia. 1983 Jan;24(1):13–15. doi: 10.1007/BF00275940. [DOI] [PubMed] [Google Scholar]
  22. Moss H. E., Burnstock G. A comparative study of electrical field stimulation of the guinea-pig, ferret and marmoset urinary bladder. Eur J Pharmacol. 1985 Aug 27;114(3):311–316. doi: 10.1016/0014-2999(85)90375-9. [DOI] [PubMed] [Google Scholar]
  23. Moss H. E., Lincoln J., Burnstock G. A study of bladder dysfunction during streptozotocin-induced diabetes in the rat using an in vitro whole bladder preparation. J Urol. 1987 Nov;138(5):1279–1284. doi: 10.1016/s0022-5347(17)43584-1. [DOI] [PubMed] [Google Scholar]
  24. Nergårdh A., Kinn A. C. Neurotransmission in activation of the contractile response in the human urinary bladder. Scand J Urol Nephrol. 1983;17(2):153–157. doi: 10.3109/00365598309180160. [DOI] [PubMed] [Google Scholar]
  25. Santicioli P., Gamse R., Maggi C. A., Meli A. Cystometric changes in the early phase of streptozotocin-induced diabetes in rats: evidence for sensory changes not correlated to diabetic neuropathy. Naunyn Schmiedebergs Arch Pharmacol. 1987 May;335(5):580–587. doi: 10.1007/BF00169128. [DOI] [PubMed] [Google Scholar]
  26. Sibley G. N. A comparison of spontaneous and nerve-mediated activity in bladder muscle from man, pig and rabbit. J Physiol. 1984 Sep;354:431–443. doi: 10.1113/jphysiol.1984.sp015386. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Taira N. The autonomic pharmacology of the bladder. Annu Rev Pharmacol. 1972;12:197–208. doi: 10.1146/annurev.pa.12.040172.001213. [DOI] [PubMed] [Google Scholar]
  28. Tomlinson D. R., Moriarty R. J., Mayer J. H. Prevention and reversal of defective axonal transport and motor nerve conduction velocity in rats with experimental diabetes by treatment with the aldose reductase inhibitor Sorbinil. Diabetes. 1984 May;33(5):470–476. doi: 10.2337/diab.33.5.470. [DOI] [PubMed] [Google Scholar]
  29. Yue D. K., Hanwell M. A., Satchell P. M., Turtle J. R. The effect of aldose reductase inhibition on motor nerve conduction velocity in diabetic rats. Diabetes. 1982 Sep;31(9):789–794. doi: 10.2337/diab.31.9.789. [DOI] [PubMed] [Google Scholar]
  30. Zar M. A., Iravani M. M., Luheshi G. N. Effect of nifedipine on the contractile responses of the isolated rat bladder. J Urol. 1990 Apr;143(4):835–839. doi: 10.1016/s0022-5347(17)40112-1. [DOI] [PubMed] [Google Scholar]

Articles from British Journal of Pharmacology are provided here courtesy of The British Pharmacological Society

RESOURCES