Objective—To determine the phosphodiesterase (PDE) isoenzymes in equine platelets and evaluate their influence on platelet adhesion.
Sample Population—Platelets obtained from healthy New Forest Pony geldings that ranged from 12 to 20 years of age (mean ± SEM, 17.3 ± 1.1 years).
Procedures—PDE isoenzyme activity in equine platelets was determined by use of a 2-step radioactive assay. Functional importance of PDE isoenzymes was established by use of selective inhibitors in a colorimetric adhesion assay.
Results—PDE1, PDE2, PDE3, and PDE5 and small amounts of PDE4 were found in equine platelets. Inhibition of PDE3 abolished platelet adhesion almost completely, whereas inhibition of PDE4 and PDE5 had little effect.
Conclusions and Clinical Relevance—Function of equine platelets can be influenced by inhibition of PDE3. Selective PDE3 inhibitors may be clinically useful to regulate platelet function. They offer the advantage of increased potency with fewer adverse effects, compared with those for nonselective PDE inhibitors.
Objective—To determine whether expression of equine platelet activation–dependent surface markers is influenced by phospodiesterase (PDE) isoenzyme activity and whether antigen challenge alters platelet PDE activity in horses with recurrent airway obstruction (RAO).
Procedures—7 healthy horses were used for in vitro experiments, 6 horses with RAO were used for antigen challenge, and 6 healthy horses were used as control animals. Three of the healthy horses had also been used in the in vitro experiments. Effects of PDE inhibition and activation of adenylyl cyclase on CD41/61 and CD62P expression on platelets and platelet-neutrophil aggregate formation in vitro were investigated via flow cytometry. Platelet PDE activity and sensitivity to inhibition of PDE3 and PDE5 isoenzymes were examined in horses with RAO and control horses before and after antigen challenge.
Results—Inhibition of PDE or activation of adenylyl cyclase significantly inhibited stimulus-induced expression of CD41/61 and CD62P (by approx 94% and 40%, respectively) and percentage of CD62P positive cells (by approx 30%). Only the PDE3 inhibitor, trequinsin, caused a significant (53%) reduction in platelet-neutrophil aggregate formation. Platelet PDE activity decreased following antigen challenge in RAO-affected horses and control horses. In horses with RAO, a significant increase in sensitivity of platelet PDE to inhibition by the PDE5 inhibitor zaprinast was observed after 5 hours.
Conclusions and Clinical Relevance—Results provided further evidence that PDE3 is an important regulator of equine platelet activation and suggested that changes in regulation of platelet PDE5 may contribute to antigen-induced response in horses with RAO.