Expression of the serotonin 1b receptor in experimental pulmonary hypertension.
The pathogenesis of pulmonary arterial hypertension (PAH) remains uncertain. Both the serotonin and endothelin (ET) systems are believed to be involved. Recent studies pointed to the importance of the serotonin 2B receptor as a limiting step. The current authors investigated the lung tissue expression of serotonin receptors and of the serotonin transporter (5-HTT) by real-time-quantitative polymerase chain reaction in chronic overcirculation-induced PAH in growing piglets, with and without treatment with the dual ET receptor blocker bosentan. Pulmonary haemodynamic changes were described by pulmonary arterial impedance spectra. Three months after the surgical anastomosis of the left subclavian artery to the pulmonary arterial trunk, there was a shift of the impedance spectra to higher ratios of pressure and flow moduli, with increases in both 0 Hz impedance and characteristic impedance, and these changes were completely prevented by bosentan therapy. There was an increase in the expression of the serotonin 1B receptor. There was no change in the expression of the 5-HTT, and of the serotonin 2B, 1D, and 4 receptors. The overexpression of the serotonin 1B receptor was partially prevented by bosentan therapy. The present authors conclude that this early pulmonary arterial hypertension model is characterised by an endothelin receptor-dependent increased expression of the serotonin 1B receptor.
D000818:Animals; D000959:Antihypertensive Agents / Q000627:therapeutic use; D000077300:Bosentan; D002352:Carrier Proteins / Q000096:biosynthesis; D006976:Hypertension, Pulmonary / Q000188:drug therapy / Q000378:metabolism*; D008168:Lung / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D016133:Polymerase Chain Reaction; D011652:Pulmonary Circulation; D044302:Receptor, Serotonin, 5-HT1B / Q000096:biosynthesis*; D017466:Receptors, Endothelin / Q000502:physiology; D012701:Serotonin / Q000378:metabolism; D050486:Serotonin Plasma Membrane Transport Proteins; D013449:Sulfonamides / Q000627:therapeutic use; D013552:Swine
D000959:Antihypertensive Agents; D002352:Carrier Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D044302:Receptor, Serotonin, 5-HT1B; D017466:Receptors, Endothelin; D050486:Serotonin Plasma Membrane Transport Proteins; D013449:Sulfonamides; D012701:Serotonin; D000077300:Bosentan