title: Peripheral vascular and neuronal effects of dopamine receptor agonists. A comparison with receptor binding studies in rat striatum.
abstract: A series of dopamine (DA)-receptor agonists was tested in vitro on vascular DA1- and neuronal DA2-receptors and the activity observed was compared to their ability to compete with [3H]-SCH23390 and [3H]-domperidone binding to rat striatal membranes. In rabbit splenic artery, where the presence of the DA1-receptor is established, DA and related agonists produced a complete concentration-dependent relaxation of the thromboxane A2-mimetic U46619-induced tone in IBMX (3-isobutyl-1-methylxanthine) treated preparations. The DA vasorelaxant effect proved to be mediated by DA1-receptors, being inhibited by the selective DA1-receptor antagonist SCH23390. Fenoldopam proved to be the most potent agonist in the rabbit splenic artery consistent with the result obtained in the D1-receptor binding assay. Epinine was about 5 times more potent than DA and only 3 times less active than fenoldopam on DA1-receptors although the D1-receptor binding study did not reveal major differences from DA. An opposite profile was observed with N,N-di-n-propyl dopamine (DPDA) showing a functional potency lower than that expected from the binding assay. In cat right atrium, DA and related agonists caused concentration-dependent inhibition of the tachycardia induced by electrical stimulation. The DA effects proved to be mediated by presynaptic DA2-receptor activation, being inhibited by the selective DA2-receptor antagonist domperidone. The DA2-receptor agonist 6-(di-n-propylamino)-5,6,7,8-tetrahydro-1,2-naphthalenediol (DP-5,6-ADTN) was the most potent compound both in the cat atrium and in the binding assay. Epinine was 2 times more potent than DA on DA2-receptors but it showed no differences in the D2-receptor binding assay.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Simes Cardiovascular Research Centre, Zambon Group, Milan, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Semeraro
authors.forename: R
authors.initials: R
authors.lastname: Ferrini
authors.forename: L
authors.initials: L
authors.lastname: Allievi
authors.forename: F
authors.initials: F
authors.lastname: Pocchiari
authors.forename: S
authors.initials: S
authors.lastname: Nicosia
authors.forename: C
authors.initials: C
authors.lastname: Casagrande
mesh_terms: D000818:Animals; D001552:Benzazepines / Q000378:metabolism; D002415:Cats; D003342:Corpus Striatum / Q000187:drug effects*; D004294:Domperidone / Q000378:metabolism; D015259:Dopamine Agents / Q000378:metabolism / Q000494:pharmacology*; D004558:Electric Stimulation; D005260:Female; D006325:Heart Atria / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D009474:Neurons / Q000187:drug effects*; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000187:drug effects* / Q000378:metabolism; D013157:Splenic Artery / Q000187:drug effects*; D014316:Tritium
chemical_list: D001552:Benzazepines; D015259:Dopamine Agents; D011954:Receptors, Dopamine; D014316:Tritium; D004294:Domperidone