C3a-induced contraction of guinea pig ileum consists of two components: fast histamine-mediated and slow prostanoid-mediated.
Guinea pig ileum is the classical experimental model for assessing the biological activity of complement-derived anaphylatoxins. Nevertheless, it is still at issue whether C3a-induced ileal contraction is entirely dependent on histamine release. We report that the contraction of the intestinal smooth muscle in response to C3a is characterized by two components, fast and slow, whose incidence and amplitude is strictly dependent on C3a concentration; the larger the concentration of C3a, the greater the incidence and magnitude of the fast component and the less frequent the slow component. The fast and slow components were characterized by a sigmoid and bell-shaped concentration-response curve, respectively. The fast component was associated with the release of endogenous histamine, increased in magnitude with the quantity of histamine released and was prevented by the histamine H1 receptor antagonist pyrilamine. On the contrary, there was no correlation between the quantity of histamine released by C3a and the magnitude of the slow component. Instead, the slow component was associated with the release of PGE2 and was prevented by the cyclooxygenase inhibitor indomethacin. Neither component was affected by the leukotriene receptor antagonist FPL 55712. Our data indicate that C3a-induced ileal contraction is partially histamine dependent in that histamine mediates only the fast component, whereas cyclooxygenase metabolites are responsible for the slow component.
del Balzo
U
U
Department of Pharmacology, Cornell University Medical College, New York, New York.
Polley
M J
MJ
Levi
R
R
D000818:Animals; D003176:Complement C3 / Q000494:pharmacology*; D015926:Complement C3a; D006168:Guinea Pigs; D006632:Histamine / Q000502:physiology*; D006636:Histamine Release; D007082:Ileum / Q000187:drug effects / Q000502:physiology; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D015289:Leukotrienes / Q000502:physiology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects*; D011453:Prostaglandins / Q000502:physiology*
D003176:Complement C3; D015289:Leukotrienes; D011453:Prostaglandins; D015926:Complement C3a; D006632:Histamine; D007213:Indomethacin