Biochemical and functional identification of a novel dopamine receptor subtype in rat brown adipose tissue. Its role in modulating sympathetic stimulation-induced thermogenesis.
Various dopamine (DA) agonists including propylnorapomorphine, lisuride, bromocriptine, apomorphine and quinpirole were found to reduce adenylate cyclase activity in rat brown adipose tissue homogenates. These inhibitory effects were antagonized, with a very low stereoselectivity, by DA receptor antagonists with the following rank order of potency: haloperidol > (+)-butaclamol > or = (-)-butaclamol >> clozapine > or = (-)-sulpiride > or = (+)-sulpiride > or = eticlopride, but not by the alpha-2 adrenoceptor antagonists, phenoxybenzamine and yohimbine or the serotonin receptor antagonists, ketanserin and metergoline. The selective D1 agonist, fenoldopam, was completely inactive in modifying the basal enzyme activity. DA as well as various DA agonists (lisuride > propylnorapomorphine > bromocriptine > apomorphine > quinpirole) dose-dependently reduced the stimulation of adenylate cyclase activity induced either by forskolin or by the beta adrenoceptor agonist, (-)-isoproterenol. Similar results were obtained also in dispersed brown adipocytes. We also found that DA and various DA receptor agonists induced a significant decrease of beta adrenoceptor-stimulated glycerol and nonesterified fatty acids release from brown adipocytes. This effect was selectively antagonized by haloperidol and butaclamol. Thus, the receptors present on the BAT membranes appear to be dopaminergic in nature although they differ from the classical D2 receptor for the following: 1) the low affinity for the most selective D2, D3 and D4 receptor agonist and antagonist (quinpirole, sulpiride and clozapine); 2) the absence of stereoselectivity for various DA antagonists (butaclamol and sulpiride); and 3) the lack of detectable mRNA encoding D2 or D3 DA receptors.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Biomedical Sciences and Biotechnologies, School of Medicine, University of Brescia, Italy.
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D000262:Adenylyl Cyclases / Q000378:metabolism; D002001:Adipose Tissue, Brown / Q000166:cytology / Q000378:metabolism*; D000818:Animals; D001483:Base Sequence; D001833:Body Temperature Regulation; D005576:Colforsin / Q000037:antagonists & inhibitors / Q000494:pharmacology; D000242:Cyclic AMP / Q000032:analysis; D015259:Dopamine Agents / Q000494:pharmacology*; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D005990:Glycerol / Q000378:metabolism; D008066:Lipolysis / Q000187:drug effects; D008090:Lisuride / Q000494:pharmacology; D008297:Male; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D011943:Receptors, Adrenergic, beta / Q000187:drug effects; D011954:Receptors, Dopamine / Q000145:classification / Q000187:drug effects* / Q000378:metabolism
D015259:Dopamine Agents; D005230:Fatty Acids, Nonesterified; D012333:RNA, Messenger; D011943:Receptors, Adrenergic, beta; D011954:Receptors, Dopamine; D005576:Colforsin; D000242:Cyclic AMP; D008090:Lisuride; D000262:Adenylyl Cyclases; D005990:Glycerol