Release of substance P from guinea pig trachea leukotriene D4.
Coordinated studies of leukotriene D4 (LTD4)-mediated contractile responses and LTD4-evoked release of the tachykinin substance P (SP) in both intact and epithelium abraded guinea pig tracheal smooth muscle preparations were performed. A partial contribution by axon reflex mechanisms to the magnitude of LTD4-induced tracheal contractions was suggested by a maximum inhibition of 21% and 28% by 5 x 10(-6) M tetrodotoxin (TTX) in abraded and intact preparations, respectively. SP-induced contractions were antagonized by the SP analog [DPro4DTrp7,9]-SP 4-11 in both types of preparation. The SP analog produced 58% and 72% inhibition of contractile responses to 10(-8) M LTD4 in abraded and intact preparations, respectively. Direct measurement of SP release by radioimmunoassay of the bathing medium showed TTX-sensitive LTD4-evoked release of SP. Inhibition by 5 x 10(-6) M TTX of LTD4-evoked SP release was 77%. The SP antagonist produced greater inhibition of LTD4-evoked contractions (58% in abraded, and 72% in intact preparations) than maximum TTX inhibition of LTD4-evoked contractions (21% in abraded, and 28% in intact). However, LTD4 (10(-8) M)-evoked SP release was at least 77% blocked by maximum doses of TTX. We therefore suggest that an additional agent, released by TTX-insensitive mechanisms, but whose contractile effects are also antagonized by [DPro4DTrp7,9]-SP 4-11, may participate in the LTD4 response.
Bloomquist
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EI
Department of Physiology, Tufts University School of Medicine, Boston, MA 02111.
Kream
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RM
D000818:Animals; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D010446:Peptide Fragments / Q000494:pharmacology; D011863:Radioimmunoassay; D013189:SRS-A / Q000494:pharmacology*; D013373:Substance P / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology; D014132:Trachea / Q000187:drug effects* / Q000378:metabolism
D010446:Peptide Fragments; D013189:SRS-A; D013373:Substance P; D013779:Tetrodotoxin; C045505:substance P (4-11), Pro(4)-Trp(7,9)-