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Leukotriene D4 acts in part to contract guinea pig ileum smooth muscle by releasing substance P.

The role of neurotransmitter release in generation of the contractile response to leukotriene D4 (LTD4) by guinea pig ileum longitudinal smooth muscle preparations was studied. The contractile response to LTD4 was inhibited partially by tetrodotoxin (TTx) with early portions of the contraction being more sensitive to inhibition by TTx. This finding suggests that part of the LTD4 contraction is mediated by release of a neurotransmitter as a result of activation of Na+-dependent action potentials. Three approaches, study of the effects of substance P (SP) desensitization and of the effects of a SP antagonist on the LTD4 response and direct measurement of SP release were used to evaluate the possibility that SP is released by LTD4. Partial inhibition of the LTD4 contraction by SP desensitization, and by the SP antagonist, as well as direct measurement of TTx sensitive SP release in the presence of LTD4, indicates that SP is released from neurons by LTD4 in guinea pig ileum.