Related Experiment Videos
Thromboxane receptor activation during bronchospasm induced by platelet-activating factor
W A Schumacher1, T E Steinbacher
1Department of Pharmacology, Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, New Jersey, 08543-4000.
Journal of Lipid Mediators
|July 1, 1991
Summary
Thromboxane receptor antagonists partially blocked platelet-activating factor (PAF) effects on lung function in guinea pigs. However, these antagonists did not prevent all PAF-induced responses, suggesting a complex role in vivo.
Area of Science:
- Pharmacology
- Respiratory Physiology
Background:
- Platelet-activating factor (PAF) is a potent mediator involved in inflammation and bronchoconstriction.
- The role of thromboxane receptors in mediating PAF's in vivo effects remains incompletely understood.
Purpose of the Study:
- To investigate the involvement of thromboxane receptors in the physiological responses induced by PAF in anesthetized guinea pigs.
Main Methods:
- Anesthetized guinea pigs were administered PAF intravenously or via intratracheal aerosol.
- Effects on dynamic lung compliance (Cdyn) and airways resistance (Rlung) were measured.
- Animals were pretreated with a thromboxane receptor antagonist (SQ 30,741), aspirin, or vehicle.
Main Results:
- SQ 30,741 and aspirin significantly blocked PAF-induced bronchospasm (reduced Cdyn, increased Rlung) following intravenous PAF administration.
- Neither drug prevented bronchospasm when higher doses of intravenous PAF were used.
- Intratracheal PAF-induced lung responses were not affected by SQ 30,741.
- Intravenous PAF-induced decreases in platelets were antagonized by SQ 30,741.
Conclusions:
- Thromboxane receptor activation contributes to certain systemic effects of blood-borne PAF in vivo.
- The contribution of thromboxane receptors to PAF's pulmonary effects appears route-dependent.
- Further research is needed to elucidate the complete mechanisms of PAF signaling in the respiratory system.