The NK‐1 Receptor and a Calcium‐Phospholipid Pathway: Inositol Trisphosphate Production and Calcium Movements Induced by Selective Agonists of Neurokinin Receptors in Rat Parotid Glands

: In the rat parotid gland, substance P has been shown to induce a phosphatidylinositol bisphosphate breakdown resulting in an inositol trisphosphate production. These data suggested that substance P activated a phospholipase C and thus mediated its effects through the calcium‐phospholipid pathway. To determine which neurokinin (NK) receptor was involved in the substance P response, we have used selective agonists of the different NK receptors and examined their effects on both inositol trisphosphate production and calcium movements. A selective NK‐1 receptor agonist, [Sar9Met(O2)11]‐substance P, evoked an [3H]inositol trisphosphate production and a rapid and transient 45Ca2+ efflux. On the other hand, selective NK‐2 and NK‐3 receptor agonists, [β‐Ala8]‐NKA(4‐10) and [MePhe7]‐NKB, respectively, were without effect. We conclude that, in the rat parotid glands, only the NK‐1 receptors are coupled to the calcium‐phospholipid pathway. The C‐terminal part of substance P appeared to be sufficient to stimulate this route because the C‐terminal octapeptide, substance P(4‐l 1), mimicked substance P effects on both inositol trisphosphate production and calcium movements. The NK‐2 and NK‐3 receptors, if present in the rat parotid glands, are not associated with the calcium‐phospholipid pathway.