Downregulation of Myocardial / 3 - Adrenergic Receptors Receptor Subtype Selectivity Kathryn

T he desensitization (loss of response) and downregulation (loss of receptors) of p-adrenergic receptors (,BAR) have been observed in several cardiac conditions, including certain forms of heart failure and hypertension. The inability of the failing heart to respond to inotropic agents such as catecholamines represents a major clinical problem. The downregulation of 131AR associated with certain forms of heart failure1 has been considered a consequence of the chronic high plasma catecholamine levels associated with this disorder. The purpose of this review is to examine agonist-induced downregulation of myocardial ,6AR in light of studies suggesting that f31AR are more resistant to downregulation than are /2AR. Potential mechanisms for differential downregulation of flAR subtypes will also be discussed, including the possibility that f82AR on cardiac myocytes are downregulated via coated pits but that f31AR are associated with plasmalemmal vesicles known as caveolae.