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. 1984 May;82(1):161–164. doi: 10.1111/j.1476-5381.1984.tb16454.x

Desensitization of the guinea-pig urinary bladder by the enantiomers of adenylyl 5'-(beta, gamma-methylene)-diphosphonate and by substance P.

S M Hourani
PMCID: PMC1987264  PMID: 6203588

Abstract

Adenosine 5'-triphosphate (ATP), substance P (SP) and non-cholinergic nerve stimulation contracted the guinea-pig urinary bladder. SP and two poorly-degradable analogues of ATP, the enantiomers of adenylyl 5'-(beta, gamma-methylene)-diphosphonate (AMP-PCP and L-AMP-PCP), were used to desensitize the guinea-pig bladder. Desensitization of the bladder by AMP-PCP (50 microM) or by L-AMP-PCP (50 microM) abolished the responses to ATP, and inhibited the responses to non-cholinergic nerve stimulation and to SP. The responses to histamine were unaffected. Desensitization by SP (1 microM) inhibited the responses to SP itself, but not the responses to ATP, L-AMP-PCP or non-cholinergic nerve stimulation. These results suggest that SP may act partly by releasing ATP, and support the suggestion that ATP rather than SP is the non-cholinergic stimulatory transmitter.

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Selected References

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  1. Alm P., Alumets J., Brodin E., Håkanson R., Nilsson G., Sjöberg N. O., Sundler F. Peptidergic (substance P) nerves in the genito-urinary tract. Neuroscience. 1978;3(4-5):419–425. doi: 10.1016/0306-4522(78)90044-1. [DOI] [PubMed] [Google Scholar]
  2. Ambache N., Killick S. W., Woodley J. P. Evidence against purinergic motor transmission in guinea-pig urinary bladder [proceedings]. Br J Pharmacol. 1977 Nov;61(3):464P–464P. [PMC free article] [PubMed] [Google Scholar]
  3. 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]
  4. Brown C. M., Burnstock G. The structural conformation of the polyphosphate chain of the ATP molecule is critical for its promotion of prostaglandin biosynthesis. Eur J Pharmacol. 1981 Jan 5;69(1):81–86. doi: 10.1016/0014-2999(81)90604-x. [DOI] [PubMed] [Google Scholar]
  5. 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]
  6. 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]
  7. Chahl L. A. Evidence that the contractile response of the guinea-pig ileum to capsaicin is due to substance P release. Naunyn Schmiedebergs Arch Pharmacol. 1982 Jun;319(3):212–215. doi: 10.1007/BF00495867. [DOI] [PubMed] [Google Scholar]
  8. Cusack N. J., Hourani S. M. Some pharmacological and biochemical interactions of the enantiomers of adenylyl 5'-(beta, gamma-methylene)-diphosphonate with the guinea-pig urinary bladder. Br J Pharmacol. 1984 May;82(1):155–159. doi: 10.1111/j.1476-5381.1984.tb16453.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Cusack N. J., Pearson J. D., Gordon J. L. Stereoselectivity of ectonucleotidases on vascular endothelial cells. Biochem J. 1983 Sep 15;214(3):975–981. doi: 10.1042/bj2140975. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Dean D. M., Downie J. W. Contribution of adrenergic and "purinergic" neurotransmission to contraction in rabbit detrusor. J Pharmacol Exp Ther. 1978 Nov;207(2):431–445. [PubMed] [Google Scholar]
  11. Husted S., Sjögren C., Andersson K. E. Substance P and somatostatin and excitatory neurotransmission in rabbit urinary bladder. Arch Int Pharmacodyn Ther. 1981 Jul;252(1):72–85. [PubMed] [Google Scholar]
  12. Kasakov L., Burnstock G. The use of the slowly degradable analog, alpha, beta-methylene ATP, to produce desensitisation of the P2-purinoceptor: effect on non-adrenergic, non-cholinergic responses of the guinea-pig urinary bladder. Eur J Pharmacol. 1982 Dec 24;86(2):291–294. doi: 10.1016/0014-2999(82)90330-2. [DOI] [PubMed] [Google Scholar]
  13. Leander S., Håkanson R., Rosell S., Folkers K., Sundler F., Tornqvist K. A specific substance P antagonist blocks smooth muscle contractions induced by non-cholinergic, non-adrenergic nerve stimulation. Nature. 1981 Dec 3;294(5840):467–469. doi: 10.1038/294467a0. [DOI] [PubMed] [Google Scholar]
  14. Lukacsko P., Krell R. D. Response of the guinea-pig urinary bladder to purine and pyrimidine nucleotides. Eur J Pharmacol. 1982 Jun 4;80(4):401–406. doi: 10.1016/0014-2999(82)90086-3. [DOI] [PubMed] [Google Scholar]
  15. Lukacsko P., Krell R. D. The effects of nucleotides on the response of the isolated guinea pig urinary bladder to nonadrenergic, noncholinergic nerve stimulation. Can J Physiol Pharmacol. 1981 Nov;59(11):1199–1201. doi: 10.1139/y81-187. [DOI] [PubMed] [Google Scholar]

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