Abstract
We investigated the activity of bombesin (BN), neuromedin-C (NM-C) and neuromedin-B (NM-B) on serotonin (5-HT) release and reuptake in rat hypothalamus (HYP) in vitro . BN and NM-C but not NM-B (all 1 μM) decreased K + evoked 3H-5-HT release from superfused HYP slices by 25%. Bacitracin (BCN, 2 μg/ml), a nonspecific peptidase inhibitor, reversed the inhibitory effect of BN on K + evoked 3H-5-HT release. Phosphoramidon (PAN, 10 μM) an endopeptidase 24.11 inhibitor, abolished the inhibitory effect of BN, but not NM-C, on K + evoked 3H-5-HT release. The peptidyl dipeptidase A inhibitor enalaprilat (ENP, 10 μM), enhanced both BN and NM-C inhibition of 3H-5-HT release. Bestatin (BST, 10 μM) had no effect on BN or NM-C inhibitory activity on 3H-5-HT release. Neither BN, NM-C nor NM-B affected reuptake of 3H-5-HT into HYP synaptosomes alone or in combination with any of the peptidase inhibitors, nor did these peptides alter the ability of fluoxetine to inhibit 3H-5-HT uptake. These data suggest: a) that BN-like peptides may alter neurotransmission in the HYP by acting presynaptically on the 5-HT release mechanisms; b) a similarity in the structural requirements for the BN induced inhibition of 5-HT release and BN evoked thermoregulatory disturbances; and c) that peptidases may selectivity augment or reduce pharmacologic activity of BN-like peptides upon CNS administration.
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