Adrenergic receptors: possible mechanism of inverse regulation of alpha- and beta-receptors.
Many physiologic and pathologic conditions, including bronchial asthma, are associated with inverse changes in alpha- and beta-receptor-mediated responses in various tissues. The direction of the change elicited by a given stimulus is tissue specific, as exemplified by the actions of thyroid hormones: In the rat heart, hypothyroidism reduces beta- and increases alpha-receptor responses, whereas in the rat liver it has the opposite effects. A similar increase in beta- and decrease in alpha-receptor responses in the rat liver is triggered by a number of different conditions, including glucocorticoid deficiency, that appear to represent lower levels of cellular differentiation. Among these, incubation of isolated hepatocytes in a serum-free buffer triggers the conversion of the receptor response in vitro within 4 hours, without parallel changes in the density or affinity of receptor binding sites. This change can be acutely reversed by an endogenous inhibitor of membrane phospholipase A2, or accelerated by an activator of phospholipase A2, suggesting that changes in the activity of this enzyme are involved in the conversion of the hepatic adrenoceptor response. The glucocorticoid-induced increase in beta-receptors in cultured human lung adenocarcinoma cells also appears to be mediated indirectly through the induction of an endogenous inhibitor (lipomodulin) of membrane phospholipase A2. The possible relevance of altered membrane phospholipid metabolism in the pathomechanism of asthma and in the associated glucocorticoid-sensitive changes in adrenergic receptor mechanisms is discussed.
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D000818:Animals; D001249:Asthma / Q000503:physiopathology; D005938:Glucocorticoids / Q000502:physiology; D006801:Humans; D008099:Liver / Q000502:physiology; D008112:Liver Glycogen / Q000378:metabolism; D010741:Phospholipases A / Q000502:physiology; D054467:Phospholipases A2; D051381:Rats; D011942:Receptors, Adrenergic, alpha / Q000502:physiology*; D011943:Receptors, Adrenergic, beta / Q000502:physiology*; D013961:Thyroid Gland / Q000502:physiology
D005938:Glucocorticoids; D008112:Liver Glycogen; D011942:Receptors, Adrenergic, alpha; D011943:Receptors, Adrenergic, beta; D010741:Phospholipases A; D054467:Phospholipases A2