Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0043167 (pertussis)
 19,595 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Relaxin produces powerful inotropic and chronotropic responses in isolated atria. The effect of relaxin has been examined in a rat model of cardiac failure, induced by myocardial infarction (MI). Maximum inotropic responses to isoprenaline (sham 5.4+/-0.3 mN; MI 2.6+/-0.3 mN; P<0.001) and relaxin (sham 5.1+/-0.6 mN; MI 2.8+/-0.5 mN; P=0.013) were reduced in left atria following MI. No change in chronotropic responsiveness was observed in right atria. Pertussis toxin (PTX) treatment restored inotropic responses to isoprenaline (sham 5.5+/-1.3 mN; MI 5.8+/-1.0 mN; P=0.850) but not to relaxin. Instead, PTX reduced inotropic responses to relaxin in sham animals to the same level seen in the MI group (sham 3.2+/-1.7 mN; MI 2.8+/-0.6 mN; P=0.847). In right atria, PTX treatment did not affect the maximum chronotropic response to isoprenaline, but reduced responses to relaxin in both sham and MI animals. R3 relaxin and relaxin receptor (LGR7) mRNA was present in atria and left ventricle (LV) from sham and MI animals. R3 relaxin mRNA expression was increased in atria but not LV from MI animals. LGR7 mRNA expression was reduced in atria and LV from MI animals. PTX treatment in unoperated rats increased chronotropic responses (vehicle 184.3+/-5.3 beats min(-1); PTX 211.3+/-9.5 beats min(-1); P=0.029) and produced a rightward shift in the concentration-response curve to isoprenaline in left atria. PTX reduced inotropic (vehicle 3.3+/-0.7 mN; PTX 0.8+/-0.2 mN; P=0.005) and chronotropic (vehicle 130.2+/-8.1 beats min(-1); PTX 90.6+/-11.1 beats min(-1); P=0.012) responses to relaxin. 6 In left atria, relaxin produced a small increase in cAMP compared to those produced by isoprenaline and forskolin. However, PTX treatment significantly reduced relaxin-, isoprenaline- and forskolin-stimulated cAMP accumulation. Cardiac failure in MI animals caused a reduced inotropic response to both relaxin and (-)-isoprenaline. In non-MI animals, PTX treatment also reduced inotropic responses to relaxin. Differences between responses to (-)-isoprenaline and relaxin can be explained by changes in coupling efficiency occurring at the level of adenylate cyclase.
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PMID:Inotropic responses to human gene 2 (B29) relaxin in a rat model of myocardial infarction (MI): effect of pertussis toxin. 1238 85

Recent studies have identified four receptors that are the physiological targets for relaxin family peptides. All are class I (rhodopsin like) G-protein-coupled receptors with LGR7 (RXFP1) and LGR8 (RXFP2) being type C leucine-rich repeat-containing receptors, whereas GPCR135 (RXFP3) and GPCR142 (RXFP4) resemble receptors that respond to small peptides such as somatostatin and angiotensin II. The cognate ligands for the receptors have been identified: relaxin for RXFP1; INSL3 for RXFP2; relaxin 3 for RXFP3 and INSL5 for RXFP4. RXFP1 and RXFP2 receptors produce increases in intracellular cAMP levels upon stimulation, although the response is complex and contains a component sensitive to PI-3-kinase inhibitors. There is also evidence that RXFP1 can activate Erk1/2 and nitric oxide synthase, and relaxin has been reported to enter cells and activate glucocorticoid receptors. In contrast, RXFP3 and RXFP4 couple to Gi by a pertussis toxin-sensitive mechanism to cause inhibition of cAMP production. Now that the receptors for relaxin family peptides and their cognate ligands have been identified, we suggest a nomenclature for both the peptides and the receptors that we hope will be helpful to researchers in this rapidly advancing field.
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PMID:Receptors for relaxin family peptides. 1595 88

Although the hormone relaxin was discovered 80 years ago, only in the past 5 years have the receptors for relaxin and three other receptors that respond to related peptides been identified with all four receptors being G-protein-coupled receptors. In this review it is suggested that the receptors for relaxin (LGR7) and those for the related peptides insulin-like peptide 3 (LGR8), relaxin-3 (GPCR135), and insulin-like peptide 5 (LGPCR142) be named the relaxin family peptide receptors 1 through 4 (RXFP1-4). RXFP1 and RXFP2 are leucine-rich repeat-containing G-protein-coupled receptors with complex binding characteristics involving both the large ectodomain and the transmembrane loops. RXFP1 activates adenylate cyclase, protein kinase A, protein kinase C, phosphatidylinositol 3-kinase, and extracellular signaling regulated kinase (Erk1/2) and also interacts with nitric oxide signaling. RXFP2 activates adenylate cyclase in recombinant systems, but physiological responses are sensitive to pertussis toxin. RXFP3 and RXFP4 resemble more conventional peptide liganded receptors and both inhibit adenylate cyclase, and in addition RXFP3 activates Erk1/2 signaling. Physiological studies and examination of the phenotypes of transgenic mice have established that relaxin has roles as a reproductive hormone involved in uterine relaxation (some species), reproductive tissue growth, and collagen remodeling but also in the cardiovascular and renal systems and in the brain. The connective tissue remodeling properties of relaxin acting at RXFP1 receptors have potential for the development of agents effective for the treatment of cardiac and renal fibrosis, asthma, and scleroderma and for orthodontic remodelling. Agents acting at RXFP2 receptors may be useful for the treatment of cryptorchidism and infertility, whereas antagonists may be used as contraceptives. The brain distribution of RXFP3 receptors suggests that actions at these receptors have the potential for the development of antianxiety and antiobesity drugs.
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PMID:International Union of Pharmacology LVII: recommendations for the nomenclature of receptors for relaxin family peptides. 1650 80