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Effect of C3a and C5a anaphylatoxins on guinea-pig isolated blood vessels.
J Pharmacol Exp Ther. 1984 Sep; 230(3):749-54.JP

Abstract

Four major guinea-pig blood vessels were isolated and studied in vitro for their contractile responses to anaphylatoxins C3a and C5a. Both peptides were assayed in the 10(-9) to 10(-7) M range and their effects were parallel, although C3a was less potent and more tachyphylactic than C5a. The most responsive blood vessel, relative to a histamine maximal response, was the portal vein, followed by the pulmonary artery and the thoracic aorta. The abdominal vena cava did not respond to either C3a or C5a. Participation of secondary mediators in the vasoconstrictor effect of C3a and C5a was assessed by exposing portal veins and pulmonary arteries to specific inhibitors. The four drugs were: indomethacin, a cyclooxygenase inhibitor; pyrilamine, an antagonist of H1 receptors for histamine; FPL55712, an antagonist of the leukotriene component of slow-reacting substance of anaphylaxis; and phentolamine, an alpha adrenergic blocker. This pharmacological analysis suggests that prostaglandin-like substances mediate most of the anaphylatoxin vasoconstrictor effects, with a biologically significant participation of leukotrienes in the case of C3a and histamine in the case of C5a. High variability between individual tissue responses to the anaphylatoxins was investigated in terms of previous exposure to activated complement. Cobra venom factor (200 micrograms) was injected i.v. in five guinea pigs 2 hr before sacrifice. This treatment reduced the serum concentration of C3 and C5 to 9 and 32%, respectively, as compared with saline-treated animals. The portal vein excised from the cobra venom factor-treated animals exhibited reduced sensitivities to C3a, but showed normal response to C5a. The selective desensitization to C3a after complement activation in vivo is presumably related to the highly tachyphylactic effect of C3a on blood vessels.

Authors

No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

6332191

Citation

Marceau, F, and T E. Hugli. "Effect of C3a and C5a Anaphylatoxins On Guinea-pig Isolated Blood Vessels." The Journal of Pharmacology and Experimental Therapeutics, vol. 230, no. 3, 1984, pp. 749-54.
Marceau F, Hugli TE. Effect of C3a and C5a anaphylatoxins on guinea-pig isolated blood vessels. J Pharmacol Exp Ther. 1984;230(3):749-54.
Marceau, F., & Hugli, T. E. (1984). Effect of C3a and C5a anaphylatoxins on guinea-pig isolated blood vessels. The Journal of Pharmacology and Experimental Therapeutics, 230(3), 749-54.
Marceau F, Hugli TE. Effect of C3a and C5a Anaphylatoxins On Guinea-pig Isolated Blood Vessels. J Pharmacol Exp Ther. 1984;230(3):749-54. PubMed PMID: 6332191.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effect of C3a and C5a anaphylatoxins on guinea-pig isolated blood vessels. AU - Marceau,F, AU - Hugli,T E, PY - 1984/9/1/pubmed PY - 1984/9/1/medline PY - 1984/9/1/entrez SP - 749 EP - 54 JF - The Journal of pharmacology and experimental therapeutics JO - J Pharmacol Exp Ther VL - 230 IS - 3 N2 - Four major guinea-pig blood vessels were isolated and studied in vitro for their contractile responses to anaphylatoxins C3a and C5a. Both peptides were assayed in the 10(-9) to 10(-7) M range and their effects were parallel, although C3a was less potent and more tachyphylactic than C5a. The most responsive blood vessel, relative to a histamine maximal response, was the portal vein, followed by the pulmonary artery and the thoracic aorta. The abdominal vena cava did not respond to either C3a or C5a. Participation of secondary mediators in the vasoconstrictor effect of C3a and C5a was assessed by exposing portal veins and pulmonary arteries to specific inhibitors. The four drugs were: indomethacin, a cyclooxygenase inhibitor; pyrilamine, an antagonist of H1 receptors for histamine; FPL55712, an antagonist of the leukotriene component of slow-reacting substance of anaphylaxis; and phentolamine, an alpha adrenergic blocker. This pharmacological analysis suggests that prostaglandin-like substances mediate most of the anaphylatoxin vasoconstrictor effects, with a biologically significant participation of leukotrienes in the case of C3a and histamine in the case of C5a. High variability between individual tissue responses to the anaphylatoxins was investigated in terms of previous exposure to activated complement. Cobra venom factor (200 micrograms) was injected i.v. in five guinea pigs 2 hr before sacrifice. This treatment reduced the serum concentration of C3 and C5 to 9 and 32%, respectively, as compared with saline-treated animals. The portal vein excised from the cobra venom factor-treated animals exhibited reduced sensitivities to C3a, but showed normal response to C5a. The selective desensitization to C3a after complement activation in vivo is presumably related to the highly tachyphylactic effect of C3a on blood vessels. SN - 0022-3565 UR - https://www.unboundmedicine.com/medline/citation/6332191/Effect_of_C3a_and_C5a_anaphylatoxins_on_guinea_pig_isolated_blood_vessels_ DB - PRIME DP - Unbound Medicine ER -