Biomaterial Database

Variable participation of 5-HT1-like receptors and 5-HT2 receptors in serotonin-induced contraction of human isolated coronary arteries. 5-HT1-like receptors resemble cloned 5-HT1D beta receptors. 1994

A J Kaumann, and M Frenken, and H Posival, and A M Brown

Clinical Pharmacology Unit, Addenbrooke's Hospital, Cambridge University, England.

BACKGROUND Serotonin may contract human large coronary arteries through two 5-hydroxytryptamine (5-HT) receptors, 5-HT1-like and 5-HT2. These 5-HT1-like receptors resemble both cloned 5-HT1D receptor subtypes, 5-HT1D alpha and 5-HT 1D beta. Although these subtypes have similar pharmacology, 5-HT1D beta receptors appear to have lower affinity for ketanserin than 5-HT1D alpha receptors. We assessed the relative participation of 5-HT1-like and 5-HT2 receptors and attempted to identify whether vasoconstrictor 5-HT1-like receptors are 5-HT1D alpha or 5-HT1D beta. RESULTS Epicardial coronary arteries were dissected from the hearts of 29 patients (including 1 healthy (donor) undergoing heart transplant operation. Endothelium-denuded strips were set up to contract at 37 degrees C. To assess the relative contributions of 5-HT1-like and 5-HT2 receptors, we blocked the latter with ketanserin (0.1 to 1.0 mumol/L) and ketanserin-resistant receptors with methiothepin (0.1 mumol/L). Concentration-effect curves for 5-HT, in the absence and presence of ketanserin, were analyzed by using a model for two receptor subtypes. The fractional contributions of 5-HT1-like and 5-HT2 receptors to the maximum effect of 5-HT, f1 and f2, were estimated in arteries from 28 patients: f1 (0.71 +/- 0.20, mean +/- SD) was significantly larger than f2 (0.29 +/- 0.20) (P < .0001). Using [3H]-serotonin to label transfected and expressed receptors, we verified that ketanserin has lower affinity for 5-HT1D beta (pKi [-log Ki, mol/L] less than 5.0) than for 5-HT1D alpha (pKi = 7.1 +/- 0.1) receptors. A concentration of ketanserin (1 mumol/L) that would occupy more than 90% of 5-HT1D alpha receptors failed to block 5-HT-induced contractions (4 patients). The 5-HT1-like receptor stimulant sumatriptan evoked maximal contractions that matched f1 and was equipotent with 5-HT through 5-HT1-like receptors (8 patients). No systematic influence of disease, atheroma, or therapy on f1 and f2 was detected. CONCLUSIONS Coronary artery contractile 5-HT1-like receptors resemble cloned 5-HT1D beta receptors and predominate over 5-HT2 receptors in mediating serotonin-evoked contractions. Sumatriptan contracts coronary arteries as a full agonist through 5-HT1-like receptors.

UI	MeSH Term	Description	Entries
D007650	Ketanserin	A selective serotonin receptor antagonist with weak adrenergic receptor blocking properties. The drug is effective in lowering blood pressure in essential hypertension. It also inhibits platelet aggregation. It is well tolerated and is particularly effective in older patients.	3-(2-(4-(4-Fluorobenzoyl)piperidinol)ethyl)-2,4(1H,3H)-quinazolinedione,R-41,468,R-41468,R 41,468,R 41468,R41,468,R41468
D008297	Male		Males
D008875	Middle Aged	An adult aged 45 - 64 years.	Middle Age
D011985	Receptors, Serotonin	Cell-surface proteins that bind SEROTONIN and trigger intracellular changes which influence the behavior of cells. Several types of serotonin receptors have been recognized which differ in their pharmacology, molecular biology, and mode of action.	5-HT Receptor,5-HT Receptors,5-Hydroxytryptamine Receptor,5-Hydroxytryptamine Receptors,Receptors, Tryptamine,Serotonin Receptor,Serotonin Receptors,Tryptamine Receptor,Tryptamine Receptors,Receptors, 5-HT,Receptors, 5-Hydroxytryptamine,5 HT Receptor,5 HT Receptors,5 Hydroxytryptamine Receptor,5 Hydroxytryptamine Receptors,Receptor, 5-HT,Receptor, 5-Hydroxytryptamine,Receptor, Serotonin,Receptor, Tryptamine,Receptors, 5 HT,Receptors, 5 Hydroxytryptamine
D002311	Cardiomyopathy, Dilated	A form of CARDIAC MUSCLE disease that is characterized by ventricular dilation, VENTRICULAR DYSFUNCTION, and HEART FAILURE. Risk factors include SMOKING; ALCOHOL DRINKING; HYPERTENSION; INFECTION; PREGNANCY; and mutations in the LMNA gene encoding LAMIN TYPE A, a NUCLEAR LAMINA protein.	Cardiomyopathy, Congestive,Congestive Cardiomyopathy,Dilated Cardiomyopathy,Cardiomyopathy, Dilated, 1a,Cardiomyopathy, Dilated, Autosomal Recessive,Cardiomyopathy, Dilated, CMD1A,Cardiomyopathy, Dilated, LMNA,Cardiomyopathy, Dilated, With Conduction Defect 1,Cardiomyopathy, Dilated, with Conduction Deffect1,Cardiomyopathy, Familial Idiopathic,Cardiomyopathy, Idiopathic Dilated,Cardiomyopathies, Congestive,Cardiomyopathies, Dilated,Cardiomyopathies, Familial Idiopathic,Cardiomyopathies, Idiopathic Dilated,Congestive Cardiomyopathies,Dilated Cardiomyopathies,Dilated Cardiomyopathies, Idiopathic,Dilated Cardiomyopathy, Idiopathic,Familial Idiopathic Cardiomyopathies,Familial Idiopathic Cardiomyopathy,Idiopathic Cardiomyopathies, Familial,Idiopathic Cardiomyopathy, Familial,Idiopathic Dilated Cardiomyopathies,Idiopathic Dilated Cardiomyopathy
D003001	Cloning, Molecular	The insertion of recombinant DNA molecules from prokaryotic and/or eukaryotic sources into a replicating vehicle, such as a plasmid or virus vector, and the introduction of the resultant hybrid molecules into recipient cells without altering the viability of those cells.	Molecular Cloning
D003327	Coronary Disease	An imbalance between myocardial functional requirements and the capacity of the CORONARY VESSELS to supply sufficient blood flow. It is a form of MYOCARDIAL ISCHEMIA (insufficient blood supply to the heart muscle) caused by a decreased capacity of the coronary vessels.	Coronary Heart Disease,Coronary Diseases,Coronary Heart Diseases,Disease, Coronary,Disease, Coronary Heart,Diseases, Coronary,Diseases, Coronary Heart,Heart Disease, Coronary,Heart Diseases, Coronary
D003331	Coronary Vessels	The veins and arteries of the HEART.	Coronary Arteries,Sinus Node Artery,Coronary Veins,Arteries, Coronary,Arteries, Sinus Node,Artery, Coronary,Artery, Sinus Node,Coronary Artery,Coronary Vein,Coronary Vessel,Sinus Node Arteries,Vein, Coronary,Veins, Coronary,Vessel, Coronary,Vessels, Coronary
D005260	Female		Females
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man