Printed in U.S.A. Coexistence of Three Tachykinin Receptors Coupled to Ca++ Signaling Pathways in Intestinal Muscle Cells1

Receptors for tachykinins and the signaling pathway to which they are coupled were characterized in dispersed muscle cells from the longitudinal muscle layer of the rat intestine. A technique of receptor protection whereby selective agonists and antago nists were used to protect one receptor while other receptors were inactivated with N-ethylmaleimide enabled each tachykinin receptor type to be identified separately. Protection of neurokinin (NK)-1 receptors with the selective NK-1 agonist, substance P methylester, or antagonist, GR-82,334 (Glp-Ala-Asp-Pro-Asn-Lys-Phe-Tyr-D-Pro[spiro-7-lactam]Leu-Trp-NH2), preserved the contractile response and increase in cytosolic-free Ca++ ([Ca++]i) induced by substance P methylester only; protection of NK-2 receptors with the selective NK-2 agonist, 0-[Alae]NKA(4-10), or the selective NK-2b antagonist, L-659,877 [cyclo(Leu