A SEPTIDE-SENSITIVE RECEPTOR IS NOT INVOLVED IN TACHYKININ-MEDIATED SECRETORY AND INOSITOL PHOSPHATE RESPONSES IN RAT PAROTID-GLAND - ARE SEVERAL TRANSDUCTION PATHWAYS INVOLVED AFTER THE STIMULATION OF THE NK1RECEPTOR

In the rat parotid gland, the neuropeptide substance P (SP), as well a s SP(4-11), and septide elicited inositol phosphate production (EC50 v alues 0.44, 2, and 20 nM, respectively), No additivity of the maximal response to the three agonists was observed. SP, SP(4-11), and septide also stimulated protein secretion; for SP, two EC50 were determined ( 0.5 and 160 nM), whereas a single one could be determined for SP(4-11) and septide (EC50 values 15 and 20 nM, respectively). The selective t achykinin NK1 receptor antagonist RP67580 acted as a competitive inhib itor of both SP-and SP(4-11)-induced inositol phosphate production. it s effect on septide-induced inositol phosphate production was noncompe titive, RP67580 is apparently as potent at antagonizing septide, SP, o r SP(4-11) (in all cases K-B = 3 nM). These results show that in parot id gland, only NK1 receptors are activated by SP, SP(4-11), and septid e. We also showed that the protein secretion stimulated by SP was inhi bited competitively by RP67580, whereas the effect of RP67580 was nonc ompetitive on protein secretion when SP(4-11) or septide was used. Our data indicate that in rat parotid gland, the existence of a specific ''septide-sensitive'' receptor can be ruled out and that only the NK1 receptor is present and mediates cellular responses. Taken together, t hese results show that in this tissue the NK1 receptor would present a t least two different binding sites that could be coupled to different transduction pathways and that would regulate protein secretion.