MECHANISMS OF SMOOTH-MUSCLE CONTRACTION ELICITED BY CATIONIC PROTEINSIN GUINEA-PIG TRACHEALIS

Cationic proteins elicit contraction of airway smooth muscle, but the mechanisms by which this occurs are not completely understood. We stud ied potential mechanisms by which eosinophil major basic protein (MBP) and the synthetic cationic proteins poly-L-lysine (PL) and poly-L-arg inine (PA) cause contraction of isolated guinea pig tracheal smooth mu scle (TSM) in vive. Topical application of 10(-8) mol/cm(2) of each pr otein to an isolated tracheal segment elicited TSM contraction with po tency PL > MBP > PA. Pretreatment with atropine blocked the subsequent response to MBP but did not block the response to either PL or PA. Pr etreatment with indomethacin blocked the subsequent response to both M BP and PL but did not block the response to PA. We demonstrate that MB P causes contraction of guinea pig TSM both through stimulation of the parasympathetic nervous system and secretion of a cyclooxygenase medi ator. 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 o n TSM in the guinea pig.