Skip to main content
Log in

Comparison of the effects of prostaglandins E2 and I2 on testicular nociceptor activities studied in vitro

  • Original Articles
  • Published:
Naunyn-Schmiedeberg's Archives of Pharmacology Aims and scope Submit manuscript

Summary

Effects of exogenous prostaglandin (PG) E2 and PGI2 on testicular polymodal receptor activities were compared in in vitro recordings of single- or multi-fiber discharges from canine testis-spermatic nerve preparations. PGI2 up to 1.4×10−6 mol/l (cumulative method) or 1.0×10−5 mol/l (non-cumulative method) excited only weakly some of the receptors, and similar observations were made with PGE2. Both PGs applied cumulatively or non-cumulatively at concentrations above 1.4×10−8 mol/l augmented the response to bradykinin (9.4×10−8 mol/l) in more than half of the cases tested. The augmenting effect of PGE2 lasted longer than that of PGI2 both with the cumulative and the non-cumulative method. The degree of augmentation tended to increase dependent on concentration, but some cases showed no further increase or rather a decrease in augmentation by PGs at a ten times higher concentration, especially when PGs were applied cumulatively. A second challenge by PG after a short interval (2 min) did not induce augmentation. These phenomena were considered to be tachyphylaxis to PGs. Cross-tachyphylaxis to PGE2 and PGI2 was also observed. There was not much difference in excitatory and augmenting potencies between these two PGs, but there was a clear difference in the concentrations of the PGs necessary to induce excitation of polymodal receptors and to facilitate their response to bradykinin.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Arturson G, Hamberg M, Jonsson C-E (1973) Prostaglandins in human burn blister fluid. Acta Physiol Scand 87:270–276

    Google Scholar 

  • Ashby B (1988) Cyclic AMP turnover in response to prostaglandins in intact platelets: evidence for separate stimulatory and inhibitory prostaglandin receptors. Second Messengers Phosphoproteins 12:45–57

    Google Scholar 

  • Ashby B (1989) Model of prostaglandin-regulated cyclic AMP metabolism in intact platelets: Examination of time-dependent effects on adenylate cyclase and phosphodiesterase activities. Mol Pharmacol 36:866–873

    Google Scholar 

  • Bessou P, Perl ER(1969) Response of cutaneous sensory units with un-myelinated fibers to noxious stimuli. J Neurophysiol 32:1025–1043

    Google Scholar 

  • Bombardieri S, Cattani P, Ciabattoni G, Di Munno O, Pasero G, Patrono C, Pinca E, Pugliese F (1981) The synovial prostaglandin system in chronic inflammatory arthritis: differential effects of steroidal and nonsteroidal antiinflammatory drugs. Br J Pharmacol 73:893–901

    Google Scholar 

  • Brodie MJ, Hensby CN, Parke A, Gordon D (1980) Is prostacyclin the major proinflammatory prostanoid in joint fluid? Life Sci 27:603–608

    Google Scholar 

  • Brown DA, Higashida H (1988) Membrane current responses of NG 108–15 mouse neuroblastoma × rat glioma hybrid cells to bradykinin. J Physiol (Loud) 397:167–184

    Google Scholar 

  • Coleman RA, Humphrey PPA, Kennedy 1, Lumley P (1984) Prostanoid receptors - the development of a working classification. Trends Pharmacol Sci 5:303–306

    Google Scholar 

  • Conklin BR, Burch RM, Steranka LR, Axelrod J (1988) Distinct bradykinin receptors mediate stimulation of prostaglandin synthesis by endothelial cells and fibroblasts. J Pharmacol Exp Ther 244:646–649

    Google Scholar 

  • Dick C, Grennan DM (1976) Studies on the relative effects of prostaglandins, bradykinin, 5-hydroxytryptamine and histamine on the synovial microcirculation in dogs. Br J Pharmacol 56:313–316

    Google Scholar 

  • Dray A, Bettaney J, Forster P, Perkins MN (1988) Bradykinin-induced stimulation of afferent fibres is mediated through protein kinase C. Neurosci Lett 91:301–307

    Google Scholar 

  • Dusting GJ, Moncada S, Vane JR (1977) Disappearance of prostacyclin in the circulation of the dog. Br J Pharmacol 62:414–415

    Google Scholar 

  • Ferreira SH (1972) Prostaglandins, aspirin-like drugs and analgesia. Nature (New Biol) 240:200–203

    Google Scholar 

  • Ferreira SH, Nakamura M, Castro MSA (1978) The hyperalgesic effects of prostacyclin and prostaglandin E2. Prostaglandins 16:31–37

    Google Scholar 

  • Higashida H, Brown DA (1986) Two polyphosphatidylinositide metabolites control two K+ currents in a neuronal cell. Nature 323:333–335

    Google Scholar 

  • Higgs EA, Moncada S, Vane JR (1978) Inflammatory effects of prostacyclin (PGI2) and 6-oxo-PGF in the rat paw. Prostaglandins 16:153–162

    Google Scholar 

  • Higgs GA, Moncada S, Salmon JA, Seager K (1983) The source of thromboxane and prostaglandins in experimental inflammation. Br J Pharmacol 79:863–868

    Google Scholar 

  • Juan H (1978) Prostaglandins as modulators of pain. Gen Pharmacol 9:403–409

    Google Scholar 

  • Juan H (1979) The pain enhancing effect of PGI2. Agents Actions 9:204–212

    Google Scholar 

  • Katori M, Harada Y, Tanaka K, Miyazaki H, Ishibashi M, Yamashita Y (1980) Changes of prostaglandin and thromboxane levels in pleural fluid of rat carrageenin-induced pleurisy. In: Samuelsson B, Ramwell W, Paoletti R (eds) Advances in prostaglandin and thromboxane research, vol 8. Raven Press, New York, pp 1733–1737

    Google Scholar 

  • Kumazawa T, Mizumura K (1980) Mechanical and thermal responses of polymodal receptors recorded from the superior spermatic nerve of dogs. J Physiol (Lond) 299:233–245

    Google Scholar 

  • Kumazawa T, Mizumura K (1984) Abnormal activity of polymodal receptors induced by clioquinol (5-chloro-7-iodo-8-hydroxyquinoline). Brain Res 310:185–188

    Google Scholar 

  • Kumazawa T, Mizumura K, Sato J (1987a) Thermally potentiated responses to algesic substances of visceral nociceptors. Pain 28:255–264

    Google Scholar 

  • Kumazawa T, Mizumura K, Sato J (1987b) Response properties of polymodal receptors studied using in vitro testis superior spermatic nerve preparations of dogs. J Neurophysiol 57:702–711

    Google Scholar 

  • Lefkowitz RJ, Stadel JM, Caron MG (1983) Adenylate cyclase-coupled beta-adrenergic receptors: structure and mechanisms of activation and desensitization. Annu Rev Biochem 52:159–186

    Google Scholar 

  • Lembeck F, Juan H (1974) Interaction of prostaglandins and indomethacin with algesic substances. Naunyn-Schmiedeberg's Arch Pharmacol 285:301–313

    Google Scholar 

  • Lewis AJ, Nelson DJ, Sygrue MF (1975) On the ability of prostaglandin E1 and arachidonic acid to modulate experimentally induced oedema in the rat paw. Br J Pharmacol 55:51–56

    Google Scholar 

  • Mense S (1981) Sensitization of group IV muscle receptors to bradykinin by 5-hydroxytryptamine and prostaglandin E2. Brain Res 225:95 -105

    Google Scholar 

  • Miller RJ (1987) Bradykinin highlights the role of phospholipid metabolism in the control of nerve excitability. Trends Neurosci 10:226–228

    Google Scholar 

  • Miller OV, Gorman RR (1979) Evidence for distinct prostaglandin I2 and D2 receptors in human platelets. J Pharmacol Exp Ther 210:134–140

    Google Scholar 

  • Mizumura K, Sato J, Kumazawa T (1986) Comparison of effects of prostaglandin-E2 and -I2 on activities of the canine visceral polymodal receptor. Nippon Seirigaku Zasshi 48:307

    Google Scholar 

  • Mizumura K, Sato J, Kumazawa T (1987) Effects of prostaglandins and other putative chemical intermediaries on the activity of canine testicular polymodal receptors studied in vitro. Pflügers Arch 408:565–572

    Google Scholar 

  • Mizumura K, Minagawa M, Tsujii Y, Kumazawa T (1990a) The effects of bradykinin agonists and antagonists on visceral polymodal receptor activities. Pain 40:221–227

    Google Scholar 

  • Mizumura K, Minagawa M, Tsujii Y, Sato J, Kumazawa T (1990b) Differences in augmenting effects of various sensitizing agents on heat and bradykinin responses of the testicular polymodal receptor. Pain 5 [Suppl]:S 135

    Google Scholar 

  • Moncada S, Flower RJ, Vane JR (1985) Prostaglandins, prostacyclin, thromboxane A2, and leukotrienes. In: Gilman AG, Goodman LS, Rall TW Murad F (eds) Goodman and Gilman's The pharmacological basis of therapeutics. Macmillan, New York, pp 661–673

    Google Scholar 

  • Osugi T, Imaizumi T, Mizushima A, Uchida S, Yoshida H (1987) Phorbol ester inhibits bradykinin-stimulated inositol triphosphate formation and calcium mobilization in neuroblastoma × glioma hybrid NG108–15 cells. J Pharmacol Exp Ther 240:617–622

    Google Scholar 

  • Roscher AA, Manganiello VC, Jelsema CL, Moss J (1984) Autoregulation of bradykinin receptors and bradykinin-induced prostacyclin formation in human fibroblasts. J Clin Invest 74:552–558

    Google Scholar 

  • Salmon JA, Higgs GA, Vane JR, Bitensky L, Chayen J, Henderson B, Cashman B (1983) Synthesis of arachidonate cyclo-oxygenase products by rheumatoid and nonrheumatoid synovial lining in non-proliferative organ culture. Ann Rheum Dis 42:36–39

    Google Scholar 

  • Schaible H-G, Schmidt RF (1988) Excitation and sensitization of fine articular afferents from cat's knee joint by prostaglandin E2. J Physiol (Lond) 403:91–104

    Google Scholar 

  • Shamma MS, Fernandez-Botran R, Suzuki T (1988) PGE2-induced desensitization of adenylate cyclase of a murine macrophage-like cell line (P388D1). Prostaglandins 36:329–341

    Google Scholar 

  • Sibley DR, Lefkowitz RJ (1985) Molecular mechanisms of receptor desensitization using the β-adrenergic receptor-coupled adenylate cyclase system as a model. Nature 317:124–129

    Google Scholar 

  • Whalley ET, Clegg S, Stewart JM, Vavrek RJ (1987) The effect of kinin agonists and antagonists on the pain response of the human blister base. Naunyn-Schmiedeberg's Arch Pharmacol 336:652–655

    Google Scholar 

  • Whittle BJR, Moncada S, Vane JR (1978) Comparison of the effects of prostacyclin (PGI2), prostaglandin E1 and D2 on platelet aggregation in different species. Prostaglandins 16:373–388

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Additional information

Send offprint requests to T. Kumazawa at the above address

Rights and permissions

Reprints and permissions

About this article

Cite this article

Mizumura, K., Sato, J. & Kumazawa, T. Comparison of the effects of prostaglandins E2 and I2 on testicular nociceptor activities studied in vitro. Naunyn-Schmiedeberg's Arch Pharmacol 344, 368–376 (1991). https://doi.org/10.1007/BF00183013

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00183013

Key words

Navigation