Evidence for cooperative binding of (-)Isoproterenol to rat brain beta1-adrenergic receptors.
In the present study, the effects of the thiol oxidising agent diamide upon the properties of rat brain beta1-adrenergic and human platelet serotonin2A receptor recognition sites have been investigated using [3H](-)CGP-12177 (in the presence of ICI-118551) and [3H]LSD as ligands. (-)Isoprenaline inhibited [3H](-)CGP-12177 binding with nH values of 0.87, 0.67, and 0.56 for added Mg2+ concentrations of 0, 2.5, and 25 mM, respectively. Pretreatment with diamide increased the nH to above unity for the inhibition of the binding by (-)isoprenaline, without a concomitant effect on the inhibition of the binding by (-)propranolol. In contrast, diamide reduced the affinity of human platelet serotonin2A-receptors for antagonists, but did not consistently induce nH values above unity for the inhibition of antagonist binding by serotonin. These results suggest that cooperative interactions reported for cardiac muscarinic receptors may also occur for beta1-adrenergic receptors in the rat brain.
Fowler
C J
CJ
Department of Pharmacology and Clinical Neuroscience, Umeâ University, Umeâ, SE-901 87, Sweden. cf@pharm.umu.se
Vedin
V
V
Sjöberg
E
E
D058665:Adrenergic beta-1 Receptor Agonists; D058671:Adrenergic beta-1 Receptor Antagonists; D000318:Adrenergic beta-Agonists / Q000378:metabolism / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000378:metabolism / Q000494:pharmacology; D000495:Allosteric Site; D000818:Animals; D001792:Blood Platelets / Q000166:cytology / Q000378:metabolism; D001921:Brain / Q000166:cytology / Q000378:metabolism*; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D003958:Diamide / Q000494:pharmacology; D004229:Dithiothreitol / Q000494:pharmacology; D004492:Edetic Acid / Q000494:pharmacology; D006801:Humans; D007545:Isoproterenol / Q000378:metabolism* / Q000494:pharmacology; D008238:Lysergic Acid Diethylamide / Q000378:metabolism; D008274:Magnesium / Q000494:pharmacology; D008970:Molecular Weight; D011412:Propanolamines / Q000037:antagonists & inhibitors / Q000378:metabolism; D051381:Rats; D044402:Receptor, Serotonin, 5-HT2A; D018342:Receptors, Adrenergic, beta-1 / Q000378:metabolism*; D011985:Receptors, Serotonin / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism / Q000494:pharmacology; D012702:Serotonin Antagonists / Q000378:metabolism / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000378:metabolism / Q000494:pharmacology
D058665:Adrenergic beta-1 Receptor Agonists; D058671:Adrenergic beta-1 Receptor Antagonists; D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D011412:Propanolamines; D044402:Receptor, Serotonin, 5-HT2A; D018342:Receptors, Adrenergic, beta-1; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D003958:Diamide; D012701:Serotonin; D008238:Lysergic Acid Diethylamide; D004492:Edetic Acid; D008274:Magnesium; D007545:Isoproterenol; C033394:CGP 12177; D004229:Dithiothreitol