Article date: August 1996
By: C.W. Emala, A. Aryana, C.A. Hirshman, in Volume 118, Issue 8, pages 2009-2016
To evaluate mechanisms involved in the impaired β‐adrenoceptor stimulation of adenylyl cyclase in tissues from the Basenji‐greyhound (BG) dog model of airway hyperresponsiveness, we compared agonist and antagonist binding affinity of β‐adrenoceptors, β‐adrenoceptor subtypes, percentage of β‐adrenoceptors sequestered, and coupling of the β‐adrenoceptor to Gsα in lung membranes from BG and control mongrel dogs. We found that lung membranes from the BG dog had higher total numbers of β‐adrenoceptors with a greater percentage of receptors of the β subtype as compared to mongrel lung membranes.
Agonist and antagonist binding affinity and the percentage of β‐adrenoceptors sequestered were not different in BG and mongrel dog lung membranes. However, the percentage of β‐adrenoceptors in the high affinity state for agonist was decreased in BG lung membranes suggesting an uncoupling of the receptor from Gsα.
Impaired coupling between the β‐adrenoceptor and G protein documented by the decreased numbers of β‐adrenoceptors in the high affinity state in BG lung membranes, is a plausible explanation for the reduced stimulation of adenylyl cyclase and the resultant reduction in airway smooth muscle relaxation in this model.
To evaluate mechanisms involved in the impaired β‐adrenoceptor stimulation of adenylyl cyclase in tissues from the Basenji‐greyhound (BG) dog model of airway hyperresponsiveness, we compared agonist and antagonist binding affinity of β‐adrenoceptors, β‐adrenoceptor subtypes, percentage of β‐adrenoceptors sequestered, and coupling of the β‐adrenoceptor to Gsα in lung membranes from BG and control mongrel dogs. We found that lung membranes from the BG dog had higher total numbers of β‐adrenoceptors with a greater percentage of receptors of the β subtype as compared to mongrel lung membranes.
Agonist and antagonist binding affinity and the percentage of β‐adrenoceptors sequestered were not different in BG and mongrel dog lung membranes. However, the percentage of β‐adrenoceptors in the high affinity state for agonist was decreased in BG lung membranes suggesting an uncoupling of the receptor from Gsα.
Impaired coupling between the β‐adrenoceptor and G protein documented by the decreased numbers of β‐adrenoceptors in the high affinity state in BG lung membranes, is a plausible explanation for the reduced stimulation of adenylyl cyclase and the resultant reduction in airway smooth muscle relaxation in this model.
DOI: 10.1111/j.1476-5381.1996.tb15637.x
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