title: Distinction between adrenergic and serotonergic receptor subtypes: specificity of drugs and absence of cooperative interactions between adrenergic and serotonergic receptor binding sites.
abstract: In light of observed amplificatory interactions between serotonergic and adrenergic stimuli in functional studies on vascular tissue and platelets, we investigated the distinction and possible interactions between alpha 1-, alpha 2-, beta 1-, and beta 2-adrenergic and 5-HT1A-, 5-HT1B-, and 5-HT2-serotonergic receptor binding sites. Therefore, the binding affinities of archetypes of adrenergic and serotonergic agonists and antagonists for the various receptors were measured. Only the alpha 1-blocker prazosin revealed great specificity for alpha 1-adrenergic receptors; the other investigated antagonists and agonists showed cross-reactivity with adrenergic and serotonergic receptors in various combinations. Using [3H]ketanserin binding to rat frontal cortex and [3H]prazosin binding to rat cortex tissue as models for 5-HT2-serotonergic and alpha 1-adrenergic receptors, respectively, we did not find cooperative effects of epinephrine on the binding of 5-hydroxytryptamine or ketanserin to 5-HT2 receptors nor of 5-hydroxytryptamine on the binding of epinephrine or prazosin to alpha 1-adrenergic receptors. It was concluded that the various adrenergic and serotonergic receptor subtypes (a) have distinct drug binding properties; (b) occur on various central and peripheral tissues; (c) co-occur on some tissues; (d) each subtype mediates several distinct functions; (e) distinct receptors may mediate similar functions; (f) the drug binding properties of a particular receptor remains the same in different tissues, but purported alpha 2-like receptors on platelets reveal some differences from alpha 2-receptors in the brain and other peripheral tissues; (g) the various receptor subtypes appear to be distinct molecular entities; and (h) in brain tissue there is no evidence for the occurrence of direct adrenergic-serotonergic receptor-receptor interactions at the level of the binding sites.
authors: Department of Biochemical Pharmacology, Janssen Research Foundation, Beerse, Belgium.
authors: J E
authors: JE
authors: Leysen
authors: P
authors: P
authors: Van Gompel
authors: W
authors: W
authors: Gommeren
mesh_terms: D000818:Animals; D001665:Binding Sites; D001667:Binding, Competitive; D002540:Cerebral Cortex / Q000378:metabolism; D004837:Epinephrine / Q000378:metabolism; D011224:Prazosin / Q000378:metabolism; D011869:Radioligand Assay; D051381:Rats; D011941:Receptors, Adrenergic / Q000032:analysis / Q000378:metabolism*; D011985:Receptors, Serotonin / Q000032:analysis / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism*; D012702:Serotonin Antagonists / Q000378:metabolism*; D013566:Sympathomimetics / Q000378:metabolism*
chemical_list: D011941:Receptors, Adrenergic; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D013566:Sympathomimetics; D012701:Serotonin; D011224:Prazosin; D004837:Epinephrine