title: Dopexamine hydrochloride in the human kidney: localization, receptor binding and effect on 3'-5'-cyclic adenosine monophosphate generation.
abstract: Dopexamine hydrochloride is a synthetic dopamine analogue recently developed to improve myocardial and renal performance in patients suffering from low cardiac output states. The present study was designed to assess the pharmacological profile and the anatomical localization of [3H]-dopexamine binding sites within the human nephron. The effects of dopexamine on the 3'-5'-cyclic adenosine monophosphate (cAMP)-generating system in membrane particles of the human kidney were also investigated. It was found that [3H]-dopexamine was specifically bound by sections of the human kidney. The binding was partly inhibited by the DA-1 receptor antagonist SCH 23390, by the beta 2-adrenoceptor antagonist ICI 118,551 and by the DA-2 receptor antagonist domperidone. The 3 antagonists in combination reduced [3H]-dopexamine binding to nonspecific values. Light microscope autoradiography revealed the accumulation of silver grains, corresponding to [3H]-dopexamine binding sites, within the different portions of the human nephron. The incubation of sections of the human kidney with [3H]-dopexamine plus SCH 23390 caused a remarkable reduction in the density of silver grains within the proximal tubule and the macula densa and a moderate decrease in the density of silver grains within the ascending and descending limbs of the loop of Henle as well as within the distal tubule. The incubation of sections of human kidney with [3H]-dopexamine plus ICI 118,551 caused a pronounced reduction in the density of silver grains within the glomerulus, the limbs of the loop of Henle, the distal tubule and the medullary collecting tubules and a moderate decrease in the density of silver grains within the macula densa and the proximal collecting tubule.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Anatomia Umana, Istituto di Farmacologia, Università di Camerino, Roma, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Napoleone
authors.forename: C
authors.initials: C
authors.lastname: Cavallotti
authors.forename: A
authors.initials: A
authors.lastname: Ricci
authors.forename: F
authors.initials: F
authors.lastname: Amenta
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000328:Adult; D000368:Aged; D001345:Autoradiography; D001552:Benzazepines / Q000494:pharmacology; D001665:Binding Sites; D001667:Binding, Competitive; D000242:Cyclic AMP / Q000096:biosynthesis*; D004298:Dopamine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000493:pharmacokinetics / Q000494:pharmacology; D015259:Dopamine Agents / Q000378:metabolism / Q000493:pharmacokinetics*; D006801:Humans; D066298:In Vitro Techniques; D007668:Kidney / Q000187:drug effects / Q000378:metabolism*; D008875:Middle Aged; D011412:Propanolamines / Q000494:pharmacology; D011869:Radioligand Assay; D018343:Receptors, Adrenergic, beta-2 / Q000187:drug effects / Q000378:metabolism; D017447:Receptors, Dopamine D1 / Q000187:drug effects / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000378:metabolism
chemical_list: D000319:Adrenergic beta-Antagonists; D001552:Benzazepines; D015259:Dopamine Agents; D011412:Propanolamines; D018343:Receptors, Adrenergic, beta-2; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; C046318:dopexamine; C026777:ICI 118551; D000242:Cyclic AMP; D004298:Dopamine