QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

The Journal of Neuroscience, May 10, 2006, 26(19):5109-5116; doi:10.1523/JNEUROSCI.3870-05.2006

This Article Full Text Full Text (PDF) Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (11) Citing Articles via Google Scholar Google Scholar Articles by Vellani, V. Articles by McNaughton, P. A. Search for Related Content PubMed PubMed Citation Articles by Vellani, V. Articles by McNaughton, P. A.

 Previous Article  |  Next Article 

Cellular/Molecular
Sensitization of Transient Receptor Potential Vanilloid 1 by the Prokineticin Receptor Agonist Bv8

Vittorio Vellani,^1,2 Mariantonella Colucci,^1,3 Roberta Lattanzi,³ Elisa Giannini,³ Lucia Negri,³ Pietro Melchiorri,³ and Peter A. McNaughton¹

¹Department of Pharmacology, University of Cambridge, Cambridge CB2 1PD, United Kingdom, ²Dipartimento di Scienze Biomediche, via Campi 287, Università degli Studi di Modena e Reggio Emilia, I-41100 Modena, Italy, and ³Dipartimento di Fisiologia Umana e Farmacologia "Vittorio Erspamer," Università di Roma "La Sapienza," 00185 Roma, Italy

Correspondence should be addressed to Peter McNaughton, Department of Pharmacology, Cambridge University, Tennis Court Road, Cambridge CB2 1PD, UK. Email: pam42{at}cam.ac.uk

Small mammalian proteins called the prokineticins [prokineticin 1 (PK1) and PK2] and two corresponding G-protein-coupled receptors [prokineticin receptor 1 (PKR1) and PKR2] have been identified recently, but the physiological role of the PK/PKR system remains mostly unexplored. Bv8, a protein extracted from frog skin, is a convenient and potent agonist for both PKR1 and PKR2, and injection of Bv8 in vivo causes a potent and long-lasting hyperalgesia. Here, we investigate the cellular basis of hyperalgesia caused by activation of PKRs. Bv8 caused increases in [Ca]_i in a population of isolated dorsal root ganglion (DRG) neurons, which we identified as nociceptors, or sensors for painful stimuli, from their responses to capsaicin, bradykinin, mustard oil, or proteases. Bv8 enhanced the inward current carried by the heat and capsaicin receptor, transient receptor potential vanilloid 1 (TRPV1) via a pathway involving activation of protein kinase C (PKC), because Bv8 caused translocation of PKC to the neuronal membrane and because PKC antagonists reduced both the enhancement of current carried by TRPV1 and behavioral hyperalgesia in rodents. The neuronal population expressing PKRs consisted partly of small peptidergic neurons and partly of neurons expressing the N52 marker for myelinated fibers. Using single-cell reverse transcriptase-PCR, we found that mRNA for PKR1 was mainly expressed in small DRG neurons. Exposure to GDNF (glial cell line-derived neurotrophic factor) induced de novo expression of functional receptors for Bv8 in a nonpeptidergic population of neurons. These results show that prokineticin receptors are expressed in nociceptors and cause heat hyperalgesia by sensitizing TRPV1 through activation of PKC. The results suggest a role for prokineticins in physiological inflammation and hyperalgesia.

Key words: pain; protein kinase; sensitization; hyperalgesia; substance P; sensory neurons; capsaicin; heat; nociception; nociceptor; TRPV

---

Received Sept. 13, 2005; revised March 13, 2006; accepted March 22, 2006.

Correspondence should be addressed to Peter McNaughton, Department of Pharmacology, Cambridge University, Tennis Court Road, Cambridge CB2 1PD, UK. Email: pam42{at}cam.ac.uk

This article has been cited by other articles:

				L. Negri, R. Lattanzi, E. Giannini, M. Colucci, F. Margheriti, P. Melchiorri, V. Vellani, H. Tian, M. De Felice, and F. Porreca Impaired nociception and inflammatory pain sensation in mice lacking the prokineticin receptor PKR1: focus on interaction between PKR1 and the capsaicin receptor TRPV1 in pain behavior. J. Neurosci., June 21, 2006; 26(25): 6716 - 6727. [Abstract] [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help