The role of 5-HT on the cardiovascular and renal systems and the clinical potential of 5-HT modulation.
The main peripheral sources of 5-hydroxytryptamine (5-HT) are as a neurotransmitter and local hormone in the gastrointestinal tract, and stored in circulating platelets and pulmonary neuroepithelial bodies. 5-HT has been shown to have many possible physiological and pathophysiological roles on the cardiovascular and renal systems. Thus, 5-HT may contribute to valvular heart disease, coronary artery disease, pulmonary hypertension, pulmonary embolism, pre-eclampsia, peripheral vascular disease and diabetic nephropathy. Consequently, modulators of the 5-HT system have diverse clinical potential. For instance, selective 5-HT subtype 3 receptor (5-HT(3)) antagonists may have potential in the treatment of the pain associated with myocardial infarction. MCI-9042 (sarpogrelate) or other 5-HT(2A) antagonists may have clinical potential for the treatment of vasospastic angina, ischaemic heart disease, reperfusion injury and hindlimb ischaemia. Several modulators of 5-HT (5-HT transporter inhibitors, 5-HT(1B) and (2B) antagonists) may have potential alone or in combination in the treatment of pulmonary hypertension. In hypertension, agonists at the 5-HT(7) and antagonists at the 5-HT(2B) may reduce blood pressure, and in diabetes, sarpogrelate may protect against nephropathy.
School of Biomedical Sciences, University of Queensland, QLD 4072, Australia. s_doggrell@yahoo.com
Sheila A
SA
Doggrell
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002320:Cardiovascular Physiological Phenomena / Q000187:drug effects*; D002352:Carrier Proteins / Q000037:antagonists & inhibitors; D003326:Coronary Circulation / Q000187:drug effects; D006321:Heart / Q000187:drug effects / Q000503:physiopathology; D006801:Humans; D007668:Kidney / Q000187:drug effects* / Q000503:physiopathology; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D016491:Peripheral Vascular Diseases / Q000188:drug therapy; D011652:Pulmonary Circulation / Q000187:drug effects; D011985:Receptors, Serotonin / Q000187:drug effects / Q000502:physiology; D012701:Serotonin / Q000502:physiology*; D018490:Serotonin Agents / Q000494:pharmacology / Q000627:therapeutic use*; D012702:Serotonin Antagonists / Q000494:pharmacology / Q000627:therapeutic use; D050486:Serotonin Plasma Membrane Transport Proteins; D017366:Serotonin Receptor Agonists / Q000494:pharmacology / Q000627:therapeutic use; D013386:Succinates / Q000494:pharmacology / Q000627:therapeutic use
D002352:Carrier Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D011985:Receptors, Serotonin; C493230:SLC6A4 protein, human; D018490:Serotonin Agents; D012702:Serotonin Antagonists; D050486:Serotonin Plasma Membrane Transport Proteins; D017366:Serotonin Receptor Agonists; D013386:Succinates; C064294:sarpogrelate; D012701:Serotonin