title: Bradykinin and prostaglandin E₁ regulate calcitonin gene-related peptide expression in cultured rat sensory neurons.
abstract: Primary cultures of adult rat dorsal root ganglia (DRG) sensory neurons were used to determine whether bradykinin and prostaglandins E₁ (PGE₁), E₂ (PGE₂) or I₂ (PGI₂) stimulate long-term calcitonin gene-related peptide (CGRP) mRNA accumulation and peptide release. Treatment (24 h) of neurons with either bradykinin or PGE₁, significantly increased CGRP mRNA content and iCGRP release. However, PGE₂ or PGI₂ was without effect. Exposure of the cultured neurons to increasing concentrations of bradykinin or PGE₁ demonstrated that the stimulation of CGRP expression was concentration-dependent, while time-course studies showed that maximal levels of CGRP mRNA accumulation and peptide release were maintained for at least 48 h. Treatment of the neuronal cultures with a bradykinin B₂ receptor antagonist significantly inhibited the bradykinin-induced increase in CGRP expression and release. In addition, preincubation of neuronal cultures with the cyclooxygenase inhibitor indomethacin did not alter the PGE₁-mediated stimulation of CGRP but blocked completely the bradykinin-induced increase in CGRP production. Therefore, these data indicate that bradykinin and PGE₁ can regulate the synthesis and release of CGRP in DRG neurons and that the stimulatory effects of bradykinin on CGRP are mediated by a cyclooxygenase product(s). Thus, these findings suggest a direct relationship between chronic alterations in bradykinin/prostaglandin production that may arise from pathophysiological causes and long-term changes in CGRP expression.
authors.affiliation: University of South Carolina School of Medicine, Department of Cell Biology and Anatomy, 6439 Garners Ferry Road, Bldg. 1, C46 Columbia, SC 29208, USA. scott.supowit@uscmed.sc.edu
authors.forename: S C
authors.initials: SC
authors.lastname: Supowit
authors.forename: H
authors.initials: H
authors.lastname: Zhao
authors.forename: K A
authors.initials: KA
authors.lastname: Katki
authors.forename: P
authors.initials: P
authors.lastname: Gupta
authors.forename: D J
authors.initials: DJ
authors.lastname: Dipette
mesh_terms: D000527:Alprostadil / Q000494:pharmacology*; D000818:Animals; D001920:Bradykinin / Q000494:pharmacology*; D015740:Calcitonin Gene-Related Peptide / Q000235:genetics / Q000378:metabolism; D018929:Cell Culture Techniques; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D015232:Dinoprostone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D011464:Epoprostenol / Q000494:pharmacology; D005727:Ganglia, Spinal / Q000187:drug effects / Q000378:metabolism*; D015870:Gene Expression / Q000187:drug effects; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D011984:Sensory Receptor Cells / Q000187:drug effects / Q000378:metabolism*; D013997:Time Factors
chemical_list: D016861:Cyclooxygenase Inhibitors; D012333:RNA, Messenger; D011464:Epoprostenol; D011451:Prostaglandin-Endoperoxide Synthases; D000527:Alprostadil; D015740:Calcitonin Gene-Related Peptide; D015232:Dinoprostone; D001920:Bradykinin; D007213:Indomethacin