title: Expression and function of serotonin 2A and 2B receptors in the mammalian respiratory network.
abstract: Neurons of the respiratory network in the lower brainstem express a variety of serotonin receptors (5-HTRs) that act primarily through adenylyl cyclase. However, there is one receptor family including 5-HT(2A), 5-HT(2B), and 5-HT(2C) receptors that are directed towards protein kinase C (PKC). In contrast to 5-HT(2A)Rs, expression and function of 5-HT(2B)Rs within the respiratory network are still unclear. 5-HT(2B)R utilizes a Gq-mediated signaling cascade involving calcium and leading to activation of phospholipase C and IP3/DAG pathways. Based on previous studies, this signal pathway appears to mediate excitatory actions on respiration. In the present study, we analyzed receptor expression in pontine and medullary regions of the respiratory network both at the transcriptional and translational level using quantitative RT-PCR and self-made as well as commercially available antibodies, respectively. In addition we measured effects of selective agonists and antagonists for 5-HT(2A)Rs and 5-HT(2B)Rs given intra-arterially on phrenic nerve discharges in juvenile rats using the perfused brainstem preparation. The drugs caused significant changes in discharge activity. Co-administration of both agonists revealed a dominance of the 5-HT(2B)R. Given the nature of the signaling pathways, we investigated whether intracellular calcium may explain effects observed in the respiratory network. Taken together, the results of this study suggest a significant role of both receptors in respiratory network modulation.
authors.affiliation: Department of Neuro- and Sensory Physiology, Georg-August-University of Göttingen, Göttingen, Germany.
authors.forename: Marcus
authors.initials: M
authors.lastname: Niebert
authors.forename: Steffen
authors.initials: S
authors.lastname: Vogelgesang
authors.forename: Uwe R
authors.initials: UR
authors.lastname: Koch
authors.forename: Anna-Maria
authors.initials: AM
authors.lastname: Bischoff
authors.forename: Miriam
authors.initials: M
authors.lastname: Kron
authors.forename: Nathalie
authors.initials: N
authors.lastname: Bock
authors.forename: Till
authors.initials: T
authors.lastname: Manzke
mesh_terms: D000818:Animals; D000906:Antibodies / Q000276:immunology; D000918:Antibody Specificity / Q000276:immunology; D002118:Calcium / Q000378:metabolism; D005453:Fluorescence; D005786:Gene Expression Regulation / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D008322:Mammals / Q000378:metabolism*; D008526:Medulla Oblongata / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D011149:Pons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D044402:Receptor, Serotonin, 5-HT2A / Q000235:genetics / Q000378:metabolism*; D044403:Receptor, Serotonin, 5-HT2B / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D015203:Reproducibility of Results; D012119:Respiration / Q000187:drug effects; D012137:Respiratory System / Q000187:drug effects / Q000378:metabolism*; D058830:Serotonin 5-HT2 Receptor Antagonists / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000906:Antibodies; D044402:Receptor, Serotonin, 5-HT2A; D044403:Receptor, Serotonin, 5-HT2B; D011994:Recombinant Proteins; D058830:Serotonin 5-HT2 Receptor Antagonists; D002118:Calcium