Alpha 1-adrenergic receptor subtypes and formation of inositol phosphates in dispersed hepatocytes and renal cells.
The ability of alpha 1a- and alpha 1b-adrenergic receptor subtypes to stimulate [3H]inositol phosphate [( 3H]InsP) formation was examined in collagenase-dispersed hepatocytes and renal cells. alpha 1-Adrenergic receptor binding sites were labeled with 125I-BE 2254, and the proportion of alpha 1a and alpha 1b subtypes was determined with chloroethylclonidine (CEC) and WB 4101. Hepatocytes contained only alpha 1b-adrenergic receptors, whereas renal cells had approximately equal proportions of both subtypes. Pretreatment of renal cells with CEC selectively inactivated the alpha 1b subtype, leaving a homogeneous population of alpha 1a receptors. Norepinephrine stimulated [3H]InsP accumulation to a similar extent in both hepatocytes and renal cells. Pretreatment with CEC inactivated this response completely in hepatocytes but only partially in renal cells. WB 4101 was 1000-fold more potent in inhibiting the [3H]InsP response in renal cells than hepatocytes; however, some of this difference was due to rapid metabolism of WB 4101 by hepatocytes. After correction for metabolism, WB 4101 was still 11-fold more potent in inhibiting norepinephrine-stimulated [3H]InsP formation in hepatocytes (alpha 1b) than in CEC-pretreated renal cells (alpha 1a). These results demonstrate that both alpha 1a- and alpha 1b-adrenergic receptor subtypes activate formation of [3H]InsP, although the molecular mechanisms by which these responses occur remain to be determined.
Han
C D
CD
Department of Pharmacology, Emory University Medical School, Atlanta, Georgia 30322.
Wilson
K M
KM
Minneman
K P
KP
D000818:Animals; D001665:Binding Sites; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D003000:Clonidine / Q000031:analogs & derivatives / Q000494:pharmacology; D066298:In Vitro Techniques; D007295:Inositol Phosphates / Q000378:metabolism*; D007668:Kidney / Q000166:cytology / Q000378:metabolism*; D008099:Liver / Q000166:cytology / Q000378:metabolism*; D009638:Norepinephrine / Q000494:pharmacology; D051381:Rats; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000378:metabolism*
D007295:Inositol Phosphates; D011942:Receptors, Adrenergic, alpha; C051731:chlorethylclonidine; D003000:Clonidine; D009638:Norepinephrine