Comparison of the densities of 5-HT4 receptors, beta 1- and beta 2-adrenoceptors in human atrium: functional implications.
We measured in human atrium the density of 5-HT4 receptors, labelled with [125I]-SB 207710 (1-butyl-4-piperidinyl) methyl 8-amino-7-iodo-1, 4-benzodioxan-5-carboxylate), and compared it with the density of beta1- and beta2-adrenoceptors, labelled with (-)-[125I]-cyanopindolol. [125I]-SB 207710 (5-1200 pmol/l) labelled a small population of saturable binding sites (Bmax approximately 4 fmol/mg protein) with a pK(D) of 9.7 and with 5-HT4 receptor characteristics, as assessed with competing ligands. The density of atrial binding sites with 5-HT4 receptor characteristics was 10 and 5 times lower, respectively, than the density of beta 1- and beta 2-adrenoceptors. We suggest that the small 5-HT4 receptor population may in part explain why the positive inotropic effects of 5-HT are smaller than those of catecholamines mediated through beta 1- and beta 2-adrenoceptors.
Kaumann
A J
AJ
Human Pharmacology Laboratory, Babraham Institute, Cambridge, UK.
Lynham
J A
JA
Brown
A M
AM
D000319:Adrenergic beta-Antagonists / Q000378:metabolism; D000328:Adult; D000368:Aged; D001667:Binding, Competitive; D002395:Catecholamines / Q000378:metabolism / Q000494:pharmacology; D004146:Dioxanes / Q000378:metabolism / Q000494:pharmacology; D006325:Heart Atria / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D007457:Iodine Radioisotopes; D007553:Isotope Labeling; D008297:Male; D008875:Middle Aged; D009200:Myocardial Contraction / Q000187:drug effects; D010869:Pindolol / Q000031:analogs & derivatives / Q000378:metabolism; D010880:Piperidines / Q000378:metabolism / Q000494:pharmacology; D018342:Receptors, Adrenergic, beta-1 / Q000187:drug effects / Q000378:metabolism*; D018343:Receptors, Adrenergic, beta-2 / Q000187:drug effects / Q000378:metabolism*; D011985:Receptors, Serotonin / Q000187:drug effects / Q000378:metabolism*; D044422:Receptors, Serotonin, 5-HT4; D012044:Regression Analysis; D012702:Serotonin Antagonists / Q000378:metabolism / Q000494:pharmacology
D000319:Adrenergic beta-Antagonists; D002395:Catecholamines; D004146:Dioxanes; D007457:Iodine Radioisotopes; D010880:Piperidines; D018342:Receptors, Adrenergic, beta-1; D018343:Receptors, Adrenergic, beta-2; D011985:Receptors, Serotonin; C088873:SB 207710; D012702:Serotonin Antagonists; D044422:Receptors, Serotonin, 5-HT4; C047975:cyanopindolol; D010869:Pindolol