Neurokinin A inhibits oxytocin and GABA release from the posterior pituitary by stimulating nitric oxide synthase

Neurokinin A (NKA) is a tachykinin that participates in the control of neur oendocrine functions. The posterior pituitary lobe (PP) contains abundant n itric oxide synthase (NOS), suggesting that nitric oxide (NO) may play a ro le in controlling the release of neuropeptides and neurotransmitters. In th e present project, we investigated the in vitro effect of NKA on oxytocin r elease from hypothalamic explants and PP of male rats and the possible invo lvement of NO in the action of NKA. Since NKA inhibits gamma -aminobutyric acid (GABA) release from PP, we also examined the role of NO in the effect of NKA on basal and K+-evoked GABA release. NKA (10(-7)-10(-5) M) significa ntly decreased oxytocin release from PP, whereas it did not affect its rele ase from hypothalamic explants. The inhibitory effect of NKA on oxytocin re lease from PP was completely blocked by the NOS inhibitors N-G-monomethyl-L -arginine (L-NMMA, 0.5 mM) or N-G-nitro-L-arginine- methyl-ester (L-NAME, 1 mM). Sodium nitroprusside (0.5 mM), an NO releaser, had no effect on basal GABA release but significantly decreased K+-evoked GABA release. L-NMMA (0 .3 mM) and L-NAME (0.5 mM) increased K+-evoked GABA release, indicating tha t NO plays an inhibitory role in GABA release from PR. The inhibition in bo th basal and K+-evoked GABA release induced by NKA (10(-7) M) was reduced b y L-NAME (1 mM). Also, NKA (10-7 M) increased NO synthesis as measured by [ C-14] citrulline production. Considered all together, our data indicate tha t NO may mediate the inhibitory effect of NKA on the release of both oxytoc in and GABA from PP. (C) 2000 Elsevier Science Inc.