Regulation of equine lymphocyte beta-adrenoceptors under the influence of clenbuterol and dexamethasone.

This research article examines the impact of two drugs, clenbuterol and dexamethasone, on the beta2-adrenoceptors of lymphocytes in horses. The study found that dexamethasone can restore and prevent the desensitisation caused by clenbuterol, suggesting that a combined therapy of these drugs may be useful for horses with chronic obstructive pulmonary disease (COPD).

Study Methodology and Results

• Twelve healthy horses were treated with two drugs; clenbuterol, a beta2-agonist, and dexamethasone, a glucocorticoid. The study aimed to understand the drug effects on lymphocyte beta2-adrenoceptor characteristics like density, affinity, and responsiveness.
• The horses were first treated with clenbuterol at a dose of 2 x 0.8 micrograms per kilogram per day intravenously for 12 days. After clenbuterol treatment, the binding sites for (-)-[125I]-iodocyanopindolol, a beta-adrenoceptor antagonist, decreased by around 30-40%. Concurrently, the response of lymphocyte cyclic AMP (cAMP – a molecule used in intracellular signal transduction) to (-)-isoprenaline decreased.
• After the stoppage of clenbuterol, there was a gradual increase in beta2-adrenoceptor density and responsiveness, reaching predrug levels after 4 days. This showed that the effect of clenbuterol on the lymphocyte’s beta2-adrenoceptors is reversible.
• The study then investigated if dexamethasone had an effect on this desensitisation caused by clenbuterol. The horses were given dexamethasone at 1 x 0.1 milligrams per kilogram per day intravenously for 5 days, immediately after stopping clenbuterol. The administration of dexamethasone hastened the recovery of beta2-adrenoceptors, restoring the number of binding sites and cAMP response to pre-clenbuterol levels within 24 hours.
• Three days after dexamethasone administration, the lymphocyte beta2-adrenoceptors were further doubled, and this increase gradually declined after dexamethasone withdrawal, reaching base levels after 4 days.
• In groups exposed to both drugs at the same time, dexamethasone completely prevented the decrease in lymphocyte beta2-adrenergic receptor density and responsiveness induced by clenbuterol.

Conclusion and Implications

• Based on the results, the study concluded that dexamethasone can reverse and prevent the desensitisation (down-regulation) of the lymphocyte’s beta2-adrenoceptors induced by clenbuterol.
• This ability to prevent desensitisation may make these drugs suitable for combined therapy in horses suffering from chronic obstructive pulmonary disease (COPD) as the density and responsiveness of beta2-adrenoceptors can be controlled.