The effect of platelet-activating factor on histamine and muscarinic receptor function in guinea pig airways.
Platelet-activating factor (PAF) administered i.v. or by aerosol to guinea pigs elicited an increase in airway responsiveness to both acetylcholine and histamine when compared with guinea pigs exposed to the vehicle bovine serum albumin (BSA). After i.v. PAF, the ED100 for acetylcholine and histamine was 5.4 and 3.4 micrograms/kg, respectively, in comparison with 17 and 6 micrograms/kg, respectively, before PAF, representing approximately a 3- and 2-fold increase in responsiveness, respectively. After aerosol PAF (500 micrograms), the ED100 for acetylcholine and histamine was 13 and 7 micrograms/kg, respectively, whereas after aerosolized BSA, the ED100 for acetylcholine and histamine was 23 and 12 micrograms/kg, respectively, representing approximately a 2-fold increase in responsiveness. However, airway smooth muscle obtained from these PAF- or BSA-treated animals did not exhibit any differences in contractile response to histamine or acetylcholine in vitro. Likewise, there were not significant differences in the binding affinity or receptor density between PAF- and BSA-treated tissues with [3H]quinuclidinylbenzilate or [3H]pyrilamine binding, which were used to identify muscarinic and H1-histamine receptors, respectively. Furthermore, histamine and carbachol-induced phosphoinositide hydrolysis was similar in PAF- and BSA-treated tracheal smooth muscle preparations. Thus, PAF induces airway hyperresponsiveness in the guinea pig that is not related to changes in airway smooth muscle or to changes in muscarinic and histamine (H1) receptor density or function.
Robertson
D N
DN
Department of Clinical Pharmacology, Cardiothoracic Institute, London, United Kingdom.
Coyle
A J
AJ
Rhoden
K J
KJ
Grandordy
B
B
Page
C P
CP
Barnes
P J
PJ
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D006632:Histamine / Q000494:pharmacology; D008168:Lung / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009119:Muscle Contraction; D010716:Phosphatidylinositols / Q000378:metabolism; D010972:Platelet Activating Factor / Q000494:pharmacology*; D011312:Pressure; D011968:Receptors, Histamine / Q000378:metabolism*; D011976:Receptors, Muscarinic / Q000502:physiology*; D012119:Respiration; D014132:Trachea / Q000187:drug effects / Q000378:metabolism*
D010716:Phosphatidylinositols; D010972:Platelet Activating Factor; D011968:Receptors, Histamine; D011976:Receptors, Muscarinic; D006632:Histamine; D000109:Acetylcholine