Biochemistry and Pharmacology of the alpha-1 Adrenergic Receptor

Bylund, David B.

doi:10.1007/978-1-4612-4582-7_2

Cited by 3 publications

(1 citation statement)

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“…The specific details for the isolation and preparation of membranes for each study parameter are given individually. For all these studies, vascular smooth muscle membranes were prepared according to the methods described by Kwan et al ., (1984) and Bylund (1987) . The preparation of vascular smooth muscle membranes involved immediate harvesting of the entire aorta from a freshly killed rat and removal of all extraneous fat tissue.…”

Section: Methodsmentioning

confidence: 99%

On the in vitro vasoactivity of bile acids

Ljubuncic

Саид

Ehrlich

et al. 2000

British J Pharmacology

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1 We compared the vasorelaxant action of nine dierent bile acids and correlated their vasorelaxant activity with their individual indices for hydrophobicity or lipophilicity. 2 Vasorelaxant activity correlated with the relative lipid solubility of bile acids with lipophilic bile acids exhibiting the greatest vasorelaxant activity with modest to no vasorelaxant activity exhibited by hydrophilic bile acids. 3 We also investigated whether bile acid-induced vasorelaxation is mediated by antagonism of a prototypal contractile receptor, the a 1 -adrenoceptor, by stimulation of a bile acid surface membrane receptor, by the release of endothelium-derived relaxant factors, by promoting the generation of reactive oxygen species and increasing the extent of lipid peroxidation, or by modifying membranē uidity. 4 Lipophilic bile acids induce vasorelaxation possibly by antagonizing a 1 -adrenoceptors, a phenomenon that manifests itself as a lowering of the anity of vascular a 1 -adrenoceptors. Bile acid-induced vasorelaxation was not dependent upon stimulation of a bile acid surface membrane receptor or the release of endothelium-derived relaxant factors. 5 Lipophilic bile acids can also increase the extent of lipid peroxidation with a subtle reduction in the¯uidity of rat vascular smooth muscle membranes not associated with loss of membrane cholesterol or phospholipid. 6 We have concluded that lipophilic bile acids are non-selective vasorelaxants whose mechanism of action is a multifaceted process involving antagonism of contractile surface membrane receptors possibly eected by an increased extent of lipid peroxidation and/or membrane¯uidity but occurs independent of the release of endothelial-derived relaxant factors or stimulation of a surface membrane bile acid binding site.

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Section: Methodsmentioning

confidence: 99%

On the in vitro vasoactivity of bile acids

Ljubuncic

Саид

Ehrlich

et al. 2000

British J Pharmacology

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Variable receptor affinity hypothesis

Bevan

Shreeve

1989

FASEB j.

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Measurements of the contractile response to norepinephrine (NE) of a variety of arteries of three mammalian species that are commonly used in the laboratory provide evidence that tissue sensitivity and affinity of the alpha 1-adrenoceptor for NE covary over a range of several orders of magnitude. The quantitative relationship suggests that variation in affinity can, to a great extent, account for the variation in sensitivity found in a number of circumstances. Furthermore, it is argued that the variation in affinity appears to be continuous and thus does not provide a basis for receptor type subdivision. There is also evidence that adrenergic antagonist affinity can vary significantly in tissues. The factors that might account for this variation include differences in receptor chemical structure, in the local membrane microenvironment, and in a number of intracellular processes. A hypothesis of variable receptor affinity has been proposed. If it is correct, then variation in receptor affinity is an important functionally relevant variable that could account for selectivity of tissue responses to circulating hormones and may represent a mechanism of change in the intact organism and in disease.

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