Direct effect of complement factor C5a on the contractile state of isolated smooth muscle cells.
The complement-(C) derived factor C5a has long been recognized as a potent contractile agonist in smooth muscle (1,2); however, controversy remains as to whether the effects of this anaphylatoxin are direct or secondary to the release of histamine (3) and/or other mediators (4-8) from nonmuscle cells within the tissue. To resolve this controversy, we have assessed the contractile effects of purified human C5a and C5a des Arg in a homogeneous preparation of enzymatically dispersed smooth muscle cells derived from the stomach of the toad, Bufo marinus. This preparation, which is insensitive to histamine at concentrations as high as 10(-4) M, responds normally to a variety of electrical (9), mechanical (10), and pharmacologic (11, 12) stimuli. These smooth muscle cells also respond to purified human anaphylatoxin; exposure to the cells to purified human C5a or C5a des Arg produce contractions of the smooth muscle cells that are accompanied by increased Ca2+ influx. The contractile response was unaffected by antagonists to histamine or acetylcholine but was reduced by 30% by pretreatment with the leukotriene antagonist FPL55712. A direct contractile effect of C5a on amphibian smooth muscle cells is suggested.
D000818:Animals; D002024:Bufo marinus; D002118:Calcium / Q000378:metabolism; D002463:Cell Membrane Permeability; D003182:Complement C5 / Q000502:physiology*; D015936:Complement C5a; D006801:Humans; D007473:Ion Channels / Q000378:metabolism; D009119:Muscle Contraction; D009130:Muscle, Smooth / Q000166:cytology / Q000502:physiology*
D003182:Complement C5; D007473:Ion Channels; D015936:Complement C5a; D002118:Calcium