Increased secretion of glandular-kallikrein in the bronchial washings induced by intravenous injection of leukotriene C4 in guinea-pigs.
1. Intravenous administration of leukotriene C4 (LTC4) and LTD4 (1-10 nmol kg-1) caused a dose-dependent increase in secretion of glandular-kallikrein in the bronchial washings of guinea-pigs, as measured by cleavage of a synthetic substrate and the formation of kinin. LTC4 was more potent than LTD4 and pilocarpine was much less potent than peptide leukotrienes on a molecular basis. 2. The increases in levels of glandular-kallikrein in the bronchial washings that were induced by LTC4 (3 nmol kg-1, i.v.) were almost completely inhibited by pretreatment with an antagonist of leukotrienes (ONO-1078), with an antagonist of thromboxane (S-1452), with an inhibitor of thromboxane synthetase (OKY-046), with indomethacin, with atropine or with scopolamine. These results indicate that the LTC4-induced increase in levels of glandular-kallikrein may have been mediated by the formation of thromboxane and the release of acetylcholine. 3. The increases in levels of glandular-kallikrein in the bronchial washings induced by STA2 (20 pmol kg-1, i.v.), a stable analogue of thromboxane A2, were completely blocked by pretreatment with atropine, whereas increases induced by pilocarpine (41 mumol kg-1, i.v.) were not blocked by pretreatment with indomethacin, although such increases were inhibited by atropine. This result indicates that secretion of kallikrein stimulated by LTC4 may have been mediated by the successive formation of thromboxane A2 and release of acetylcholine. 4. Intravenous administration of bradykinin (3-30 nmol kg-1) caused a dose-dependent increase in levels of glandular-kallikrein in the bronchial washings. This increase was completely inhibited by pretreatment with atropine, with indomethacin or with an antagonist of thromboxane.5. The increases in levels of glandular-kallikrein in the bronchial washings induced by LTC4 (3 nmol kg'- , i.v.) and pilocarpine (41 flmol kg- 1, i.v.) were significantly inhibited by pretreatment with an antagonist of bradykinin. These results suggest that intravenous LTC4 may increase secretion of glandular-kallikrein via formation of thromboxane A2 and release of acetylcholine in that order, and kinin released by kallikrein may enhance the rate of secretion of glandular-kallikrein.
Jin
H Y
HY
Department of Pharmacology, Kitasato University School of Medicine, Kanagawa, Japan.
Katori
M
M
Majima
M
M
Sunahara
N
N
D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D001920:Bradykinin / Q000037:antagonists & inhibitors / Q000494:pharmacology; D001980:Bronchi / Q000378:metabolism*; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007275:Injections, Intravenous; D007610:Kallikreins / Q000378:metabolism*; D007705:Kinins / Q000494:pharmacology; D008297:Male; D010275:Parasympathetic Nervous System / Q000187:drug effects; D010862:Pilocarpine / Q000494:pharmacology; D013189:SRS-A / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D013931:Thromboxanes / Q000037:antagonists & inhibitors / Q000096:biosynthesis
D007705:Kinins; D013189:SRS-A; D013931:Thromboxanes; D010862:Pilocarpine; D001285:Atropine; D007610:Kallikreins; D000109:Acetylcholine; D001920:Bradykinin