Mechanisms of smooth muscle contraction elicited by cationic proteins in guinea pig trachealis.
Cationic proteins elicit contraction of airway smooth muscle, but the mechanisms by which this occurs are not completely understood. We studied potential mechanisms by which eosinophil major basic protein (MBP) and the synthetic cationic proteins poly-L-lysine (PL) and poly-L-arginine (PA) cause contraction of isolated guinea pig tracheal smooth muscle (TSM) in vivo. Topical application of 10(-8) mol/cm2 of each protein to an isolated tracheal segment elicited TSM contraction with potency PL > MBP > PA. Pretreatment with atropine blocked the subsequent response to MBP but did not block the response to either PL or PA. Pretreatment with indomethacin blocked the subsequent response to both MBP and PL but did not block the response to PA. We demonstrate that MBP causes contraction of guinea pig TSM both through stimulation of the parasympathetic nervous system and secretion of a cyclooxygenase mediator. Neither PL nor PA, while of similar molecular weight and charge as MBP, cause TSM contraction via the parasympathetic nervous system, though some cationic proteins may act via a prostanoid mediator. Thus the cationic charge of MBP is not solely responsible for its effects on TSM in the guinea pig.
Strek
M E
ME
Department of Medicine, University of Chicago, Illinois 60637, USA.
Williams
F S
FS
Gleich
G J
GJ
Leff
A R
AR
White
S R
SR
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001798:Blood Proteins / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D002412:Cations / Q000494:pharmacology; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D047091:Eosinophil Granule Proteins; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects* / Q000502:physiology; D010455:Peptides / Q000494:pharmacology*; D011107:Polylysine / Q000494:pharmacology*; D012260:Ribonucleases; D014132:Trachea / Q000187:drug effects* / Q000502:physiology
D001798:Blood Proteins; D002412:Cations; D016861:Cyclooxygenase Inhibitors; D047091:Eosinophil Granule Proteins; D010455:Peptides; D011107:Polylysine; C015462:polyarginine; D001285:Atropine; D012260:Ribonucleases; D000109:Acetylcholine