The alpha 1-adrenoceptor is inactivated by alterations in membrane phospholipids.
The influence of the membrane environment on the alpha 1-adrenoceptor has been investigated by examining the effect of phospholipase digestion on the binding of [3H]prazosin to aortic and hepatic membranes. Membrane digestion by phospholipase A2 and phospholipase C was found to markedly reduce prazosin binding to the alpha 1-adrenoceptor whereas phospholipase D had comparatively little effect. In addition, there were differences between membrane preparations since the aortic alpha 1-adrenoceptor was less sensitive to phospholipase A2 and phospholipase C than the hepatic receptor. The results support a major role for hydrophobic groups and the negatively charged, hydrophilic phosphate moiety of phospholipids in the interaction between prazosin and the alpha 1-adrenoceptor.
Shreeve
S M
SM
Department of Pharmacology, College of Medicine, University of Vermont, Burlington 05405.
Valliere
J E
JE
D000818:Animals; D001011:Aorta / Q000378:metabolism; D001665:Binding Sites; D002462:Cell Membrane / Q000737:chemistry; D008099:Liver / Q000378:metabolism; D008297:Male; D008563:Membrane Lipids / Q000737:chemistry* / Q000378:metabolism; D009131:Muscle, Smooth, Vascular / Q000378:metabolism; D010741:Phospholipases A / Q000378:metabolism; D054467:Phospholipases A2; D010743:Phospholipids / Q000737:chemistry / Q000378:metabolism*; D011224:Prazosin / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011942:Receptors, Adrenergic, alpha / Q000737:chemistry / Q000378:metabolism*; D010738:Type C Phospholipases / Q000378:metabolism
D008563:Membrane Lipids; D010743:Phospholipids; D011942:Receptors, Adrenergic, alpha; D010741:Phospholipases A; D054467:Phospholipases A2; D010738:Type C Phospholipases; D011224:Prazosin