Adrenergic receptors: Possible mechanism of inverse regulation of α- and β-receptors

• Published in: Journal of Allergy and Clinical Immunology [J. ALLERGY CLIN. IMMUNOL.]. Vol. 76, no. 2 pt. 2. 1985 Vol. 76; no. 2; pp. 346 - 351
• Main Authors: Kunos, George, Kunos, Ildiko, Hirata, Fusao, Ishac, Edward J.N.
• Format: Journal Article Conference Proceeding
• Language: English
• Published: United States Mosby, Inc 01.08.1985
• Subjects: adrenergic; Animals; Asthma - physiopathology; Glucocorticoids - physiology; Humans; Liver - physiology; Liver Glycogen - metabolism; Phospholipases A - physiology; Phospholipases A2; Rats; Receptors, Adrenergic, alpha - physiology; Receptors, Adrenergic, beta - physiology; Thyroid Gland - physiology; thyroid hormones; tissues; cAMP; ADP
• ISSN: 0091-6749; 1097-6825
• DOI: 10.1016/0091-6749(85)90652-9

Many physiologic and pathologic conditions, including bronchial asthma, are associated with inverse changes in α- and β-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 β- and increases α-receptor responses, whereas in the rat liver it has the opposite effects. A similar increase in β- and decrease in α-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 A 2, or accelerated by an activator of phospholipase A 2, suggesting that changes in the activity of this enzyme are involved in the conversion of the hepatic adrenoceptor response. The glucocorticoid-induced increase in β-receptors in cultured human lung adenocarcinoma cells also appears to be mediated indirectly through the induction of an endogenous inhibitor (lipomodulin) of membrane phospholipase A 2. 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.