title: Expression and function of GDNF family ligands and receptors in the carotid body.
abstract: The carotid body is a neural crest-derived neuroendocrine organ that detects the oxygen level in blood and regulates ventilation. Unlike many other neural crest derivatives, the trophic factors mediating survival and differentiation of neuroendocrine cells of the carotid body are unknown. Given that many neural crest derivatives rely on the glial cell line-derived neurotrophic factor (GDNF) family of ligands (GFLs) for survival and function, we undertook an analysis of the carotid body as a potential site of GFL action. RET and GDNF family receptor alphas (GFRalpha) 1-3 are expressed in the developing carotid body as detected by RT-PCR and immunocytochemistry. mRNA for GDNF, and artemin (ARTN) were also present. In vitro, treatment with GDNF, neurturin (NRTN), or ARTN, individually or in combination, produced an increase in the number and length of processes of the Type-I glomus cells of the carotid body [embryonic day-17 (E17) rats]. However, GFLs alone or in combination had no effect on glomus cell survival in either postnatal day-1 (P1) or E17 carotid body cultures. These results suggest that one or more GFLs may have a role in carotid body function. In addition, the results of this study suggest that endogenous or exogenous GFLs may enhance target innervation by carotid body transplants.
authors.affiliation: Department of Molecular Biology and Pharmacology, Washington University School of Medicine, Saint Louis, MO 63110-1031, USA.
authors.forename: Melanie L
authors.initials: ML
authors.lastname: Leitner
authors.forename: Leo H
authors.initials: LH
authors.lastname: Wang
authors.forename: Patricia A
authors.initials: PA
authors.lastname: Osborne
authors.forename: Judith P
authors.initials: JP
authors.lastname: Golden
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Milbrandt
authors.forename: Eugene M
authors.initials: EM
authors.lastname: Johnson
mesh_terms: D000818:Animals; D002344:Carotid Body / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D002454:Cell Differentiation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D051100:Glial Cell Line-Derived Neurotrophic Factor; D051097:Glial Cell Line-Derived Neurotrophic Factor Receptors; D008024:Ligands; D009414:Nerve Growth Factors / Q000235:genetics* / Q000494:pharmacology; D009419:Nerve Tissue Proteins / Q000235:genetics*; D016501:Neurites / Q000187:drug effects; D051101:Neurturin; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D051096:Proto-Oncogene Proteins c-ret; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D020794:Receptor Protein-Tyrosine Kinases / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014446:Tyrosine 3-Monooxygenase / Q000096:biosynthesis
chemical_list: C490887:Artn protein, rat; C495041:Gdnf protein, rat; C494989:Gfra1 protein, rat; D051100:Glial Cell Line-Derived Neurotrophic Factor; D051097:Glial Cell Line-Derived Neurotrophic Factor Receptors; D008024:Ligands; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D051101:Neurturin; C495057:Nrtn protein, rat; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D014446:Tyrosine 3-Monooxygenase; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases; C495001:Ret protein, rat