Expression of two different tachykinin receptors in Xenopus oocytes by exogenous mRNAs.

Abstract

Three tachykinins, substance P (SP), neurokinin A (NKA), and neurokinin B (NKB), have been isolated from the mammalian nervous system. In accordance with the presence of multiple tachykinins, the existence of multiple tachykinin receptors has been suggested. These receptors differ in binding specificities for different tachykinins. However, it is not known whether these receptors are indeed made of different molecules or whether the same receptor molecule undergoes posttranslational modification at different destination tissues, thereby altering its binding specificity. We examined whether mRNAs isolated from different tissues may synthesize different types of tachykinin receptors in the same expression system. For this purpose, Xenopus oocytes were injected with poly (A)+ RNAs extracted from rat brain or bovine stomach, and their responses to different tachykinins were examined under voltage-clamp. On the basis of potency ranking of 6 tachykinin agonists, the receptor induced by rat brain mRNA was found to correspond to a tachykinin receptor subtype currently classified as the NK-1 (SP-P) receptor, whereas that synthesized by bovine stomach mRNA corresponded to the NK-2 (NK-A) receptor. Thus, each of the 2 receptors can be induced in the same expression system, depending upon the source of exogenous mRNA injected. Therefore, the difference in the nature of the 2 receptors does not seem to be due to the possible posttranslational modification alone. However, the ionic mechanisms underlying activation of the 2 receptors translated in oocytes were similar. It is likely that activation of the 2 receptors uses the same internal mediator in oocytes.