We examined basal adenosine 3',5'-cyclic monophosphate (cAMP) levels, isoproterenol (ISO)-stimulated cAMP responses, basal cAMP, and guanosine 3',5'-cyclic monophosphate (cGMP) phosphodiesterase (PDE) activities and protein-kinase (PK) activities in trachealis muscle from five Basenji-greyhound (BG) and four greyhound dogs to determine whether the inverse relationship between in vivo and in vitro airway responsiveness could be due to altered cyclic nucleotide metabolism. Basal cAMP levels were not significantly different (PNS) in muscle from BG (11.6 ± 0.53 pmol/mg protein) and greyhound dogs (10.30 ± 1.60 pmol/mg protein). The cAMP responses to stimulation with ISO were enhanced in BG compared with greyhound dogs. The low Michaelis constant (1) for K(m)-cAMP PDE activity (K(m) = 0.63 μM) was significantly less (P < 0.005) in BG dogs (1.54 ± 0.28 pmol·min-1·mg protein-1) than greyhounds (11.76 ± 2.48). Endogenously active PK activity was significantly greater (P < 0.005) in BG (54.74 ± 5.39 pmol·min-1·mg protein-1) than in greyhound dogs (15.50 ± 2.20). Increases in PK activity with 5 μM cAMP added were not significantly different between BG (14.79 ± 6.00) and greyhound dogs (7.04 ± 2.14). Approximately 90% of both endogenous PK activity and cAMP-activated PK activity in BG and greyhound dogs was inhibited by a cAMP-dependent PK inhibitor (PKI'). These data suggest that decreased cyclic nucleotide degradation due to decreased cyclic nucleotide PDE activity with increased PK could account for the in vitro hyporesponsiveness of airway smooth muscle in BG dogs as a protective adaptive mechanism.
ASJC Scopus subject areas
- Physiology (medical)