PDE8 Is Expressed in Human Airway Smooth Muscle and Selectively Regulates cAMP Signaling by β₂-Adrenergic Receptors and Adenylyl Cyclase 6.

ABSTRACT: Two cAMP signaling compartments centered on adenylyl cyclase (AC) exist in human airway smooth muscle (HASM) cells, one containing β₂-adrenergic receptor AC6 and another containing E prostanoid receptor AC2. We hypothesized that different PDE isozymes selectively regulate cAMP signaling in each compartment. According to RNA-sequencing data, 18 of 24 PDE genes were expressed in primary HASM cells derived from age- and sex-matched donors with and without asthma. PDE8A was the third most abundant of the cAMP-degrading PDE genes, after PDE4A and PDE1A. Knockdown of PDE8A using shRNA evoked twofold greater cAMP responses to 1 μM forskolin in the presence of 3-isobutyl-1-methylxanthine. Overexpression of AC2 did not alter this response, but overexpression of AC6 increased cAMP respons

SUBMITTER: Johnstone TB 

PROVIDER: S-EPMC5894499 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature