Prostaglandin E2 Enhances Bradykinin-evoked iCGRP Release in Bovine Dental Pulp

Abstract

Mediators produced during inflammation are responsible for hyperalgesia and expression of neurotransmitters and receptors in the nervous system. The production of bradykinin (BK) and the prostaglandins (PGs) may regulate initiation of pain. This study tested the hypothesis that BK and prostaglandin E₂ (PGE₂) have a positive interaction in evoking neurosecretion of immunoreactive calcitonin gene-related peptide (iCGRP). Bovine dental pulp was prepared and stimulated by the superfusion method with BK alone and in combination with PGE₂. Kinin receptor antagonists to bradykinin-evoked release of iCGRP were also tested. Also tested was the hypothesis that dental pulp contains cither the B, or B₂ or both BK receptors. Results showed that PGE₂ enhanced BK-evoked iCGRP release by more than 50%. Western immunoblots revealed detectable B, receptor protein with no detectable B₁ receptor protein. We conclude that BK evokes iCGRP release from bovine dental pulp which is enhanced by a positive interaction with PGE₂. Neurosecretion is evoked from isolated terminals of dental pulp fibers via the bradykinin B₂ receptor-dependent mechanism.

Keywords

prostaglandin E2 bradykinin pain iCGRP release.

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References

Ahlquist ML , Edwall LG , Franzen OG , Haegerstam GA (1984). Perception of pulpal pain as a function of intradental nerve activity. Pain 19:353-366.

Ahlquist ML , Franzen OG , Edwall LE , Fors UG , Haegerstam GA (1985). Quality of pain sensations following local application of algogenic agents on the exposed human tooth pulp: a psychological and electrophysiological study. In: Advances in Pain Research and Therapy. Vol. 9. Fields HL , Dubner R , Cervero F , editors. New York: Raven Press, pp. 351-359.

Anderson DJ , Matthews B. (1967). Osmotic stimulation of human dentine and the distribution of dental pain thresholds. Arch Oral Biol 12:417-426.

Andreeva L. , Rang HP ( 1993). Effect of bradykinin and prostaglandins on the release of calcitonin gene-related peptide-like immunoreactivity from the rat spinal cord in vitro. Br J Pharmacol 108:185-190.

Byers MR , Taylor PE (1993). Effect of sensory denervation on the response of rat molar pulp to exposure injury. J Dent Res 72:613-618.

Chahl LA , Iggo A. ( 1977). The effects of bradykinin and prostaglandin E, on rat cutaneous afferent nerve activity. Br J Pharmacol 59:343-347.

Costello AH , Hargreaves KM (1989). Suppression of carrageenan-induced hyperalgesia, hyperthermia and edema by a bradykinin antagonist. Eur J Pharmacol 171:259-263.

Cui M. , Nicol GD (1995). Cyclic AMP mediates the prostaglandin E2-induced potentiation of bradykinin excitation in rat sensory neurons. Neuroscience 66:459-466.

Dray A. , Patel IA , Perkins MN , Rueff A. (1992). Bradykinin-induced activation of nociceptors: receptor and mechanistic studies on the neonatal rat spinal cord-tail preparation in vitro. Br J Pharmacol 107:1129-1134.

10.

Edwall L. , Olgart L. (1977). A new technique for recording of intradental sensory nerve activity in man. Pain 3:121-125.

11.

Evans AR , Nicol GD , Vasko MR (1996). Differential regulation of evoked peptide release by voltage sensitive calcium channels in rat sensory neurons. Brain Res 712:265-273.

12.

Hargreaves KM , Bowles WR , Garry MG (1992). An in vitro method to evaluate regulation of neuropeptide release from dental pulp. J Endod 18:597-600.

13.

Holzer P. (1988). Local effector functions of capsaicin-sensitive sensory nerve endings: involvement of tachykinins, calcitonin gene-related peptide and other neuropeptides. Neuroscience 24:739-768.

14.

Holzer P. (1991). Capsaicin: cellular targets, mechanisms of action, and selectivity for thin sensory neurons. Pharmacol Rev 43:143-201.

15.

Kanmerer S. , Braun A. , Arnold N. , Roscher AA (1995). The human bradykinin B2 receptor gene: full length cDNA, genomic organization and identification of the regulatory region. Biochem Biophys Res Commun 211:226-233.

16.

Kerezoudis NP , Fried K. , Olgart L. (1995). Haemodynamic and immunohistochemical studies of rat incisor pulp after denervation and subsequent re-innervation. Arch Oral Biol 40:815-823.

17.

Menke JG , Borkowski JA , Bierilo KK , MacNeil T. , Derrick AW , Schneck KA , et al. (1994). Expression cloning of a human B1 bradykinin receptor. J Biol Chem 269:21583-21586.

18.

Nicol GD , Cui M. (1994). Enhancement by prostaglandin E2 of bradykinin activation of embryonic rat sensory neurons. J Physiol (Lond) 480:485-492.

19.

Pesquero JB , Lindsey CJ , Zeh K. , Paiva AC , Ganten D. , Bader M. (1994). Molecular structure and expression of rat bradykinin B2 receptor gene. Evidence for alternative splicing. J Biol Chem 269:26920-26925.

20.

Rueff A. , Dray A. ( 1993). Sensitization of peripheral afferent fibers in the in vitro neonatal rat spinal cord-tail by bradykinin and prostaglandins. Neuroscience 54:527-535.

21.

Stucky CL , Thayer SA , Seybold VS (1996). Prostaglandin E2 increases the proportion of neonatal rat dorsal root ganglion neurons that respond to bradykinin. Neuroscience 74:1111-1123.

22.

Teixeira MM , Williams TJ , Hellewell PG (1993). Role of prostaglandins and nitric oxide in acute inflammatory reactions in guinea-pig skin. Br J Pharmacol 110: 1515-1521.

23.

Uddman R. , Grunditz T. , Sundler F. (1986). Calcitonin gene related peptide: a sensory transmitter in dental pulps? Scand J Dent Res 94:219-224.