Norepinephrine increases angiotensin II binding in rat brain synaptosomes.
Synaptosomes prepared from rat hypothalamus or brainstem contain specific binding sites for [125I]-angiotensin II (AII). Treatment of these synaptosomes with norepinephrine (NE) (10-500 microM) for 60 min results in a concentration-dependent increase in [125I]-AII specific binding which appears to be an increase in the number rather than the affinity of these binding sites. This effect of NE is qualitatively similar in synaptosomes prepared from neonate (one-day-old) or adult (140-day-old) rats. Furthermore, it is antagonized by prazosin (10 microM) but not by yohimbine (10 microM), indicating the involvement of alpha 1-adrenergic receptors. Finally, this effect of NE may involve activation of protein kinase C (PKC) because it is mimicked by a PKC agonist (TPA, 0.8 microM; 60 min) and is blocked by a PKC antagonist (H-7, 100 microM). These results match our previous findings on the regulation of AII receptors in neurons cultured from the hypothalamus and brainstem of neonate rats and provide strong evidence for a role of this catecholamine in the modulation of brain AII receptors.
Sumners
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Department of Physiology, College of Medicine, University of Florida, Gainesville 32610.
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000804:Angiotensin II / Q000378:metabolism*; D000818:Animals; D001933:Brain Stem / Q000187:drug effects / Q000378:metabolism; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism; D066298:In Vitro Techniques; D007546:Isoquinolines / Q000494:pharmacology; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology*; D010703:Phorbol Esters / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011945:Receptors, Angiotensin / Q000187:drug effects / Q000378:metabolism; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism*
D000317:Adrenergic alpha-Antagonists; D007546:Isoquinolines; D010703:Phorbol Esters; D010879:Piperazines; D011945:Receptors, Angiotensin; D000804:Angiotensin II; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D011493:Protein Kinase C; D009638:Norepinephrine