TACHYKININS INDUCE SECRETION OF PROLACTIN FROM PERIFUSED RAT ANTERIOR-PITUITARY-CELLS BY INTERACTIONS WITH 2 DIFFERENT BINDING-SITES

Substance P and the two other mammalian tachykinins, neurokinin A and B, are accepted to have direct regulating effects at the anterior pitu itary level. We have examined the effects of substance P (SP) and neur okinin B (NKB), alone and in combination, on prolactin release from cu ltured anterior pituitary cells grown on collagen-coated micro beads a nd placed in a perfusion system. Prolactin (Prl) secretion was observe d within 25 s after exposure to either secretagogue and reached a maxi mum within 60-80 s. Furthermore, the prolactin response induced by SP and NKB was dose-dependent. Prl secretion remained constant for up to 4 h when SP or NKB were perifused and then fell gradually towards basa l levels. Simultaneous addition of submaximal concentrations of SP and NKB resulted in an additive response compared with the responses of e ither secretagogue alone. Continuous (8 h) perifusion with SP did not prevent a normal prolactin response by NKB or TRH. These results indic ate that the tachykinins, substance P and neurokinin B, release Prl fr om perifused female rat anterior pituitary cells by interaction with t wo different receptors, possibly the NK1 and NK3 tachykinin receptor s ubtypes.