Proposed model of ADMA action on alcohol-stimulated cilia beating. Alcohol (EtOH) rapidly and transiently stimulates cilia beat frequency (CBF) by both activating the alcohol-sensitive adenylyl cyclase isoform 7 (AC) and increasing the phosphorylation of heat shock protein 90 (hsp90) leading to the increased binding of hsp90 and the activation of nitric oxide synthase (eNOS). Nitric oxide (NO•) activates soluble guanylyl cyclase (GC) leading to a cGMP-dependent protein kinase (PKG) activation required for alcohol-induced activation of cAMP-dependent protein kinase (PKA). Asymmetric dimethylarginine (ADMA) functions to negatively regulate alcohol stimulation of eNOS, except under the conditions of elevated dimethylarginine dimethylaminohydrolase (DDAH) whereby ADMA is converted to L-citrulline (L-cit).
