Reversibility of tachyphylaxis to C5A in guinea pig tissues, perfused human placental lobule, and umbilical artery.
The spasmogenic effect of C5a is mediated by histamine and/or eicosanoids. Tachyphylaxis to this effect of C5a occurs rapidly, but the spasmogenic effects of C5a on a guinea pig lung parenchymal strips, field-stimulated ventricular papillary muscle, and human umbilical artery were completely restored by a 1-h period of drug-free rest, whereas that of guinea pig ileum was not. Perfusion of the isolated human placental lobule with C5a caused a transient pressor response that was largely abolished by indomethacin (5 microM), indicating mediation by cyclooxygenase metabolites. This pressor response to C5a was also completely restored following a 1-h rest period. The results show that tissue rest reverses tachyphylaxis to the spasmogenic effects of C5a in tissues where the response is mediated by cyclooxygenase metabolites. Where the response is mediated by histamine released by mast cells, restoration does not occur, presumably because of the catastrophic nature of mast cell degranulation. Histamine released in guinea pig papillary muscle by C5a may be from non-mast-cell sources.
Department of Physiology and Pharmacology, University of Queensland St. Lucia, Australia.
S M
SM
Taylor
A M
AM
Finch
A E
AE
Heron
L C
LC
Brown
T H
TH
Florin
D000818:Animals; D015936:Complement C5a / Q000494:pharmacology*; D005260:Female; D006168:Guinea Pigs; D006801:Humans; D007082:Ileum / Q000187:drug effects / Q000502:physiology; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D008168:Lung / Q000187:drug effects / Q000502:physiology; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology*; D009200:Myocardial Contraction / Q000187:drug effects / Q000502:physiology; D010210:Papillary Muscles / Q000187:drug effects / Q000502:physiology; D010920:Placenta / Q000187:drug effects / Q000502:physiology; D011247:Pregnancy; D013618:Tachyphylaxis / Q000502:physiology*; D014469:Umbilical Arteries / Q000187:drug effects / Q000502:physiology
D015936:Complement C5a; D007213:Indomethacin