Inhibition of serotonin release by bombesin-like peptides in rat hypothalamus in vitro.
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 microM) decreased K+ evoked 3H-5-HT release from superfused HYP slices by 25%. Bacitracin (BCN, 2 micrograms/ml), a nonspecific peptidase inhibitor, reversed the inhibitory effect of BN on K+ evoked 3H-5-HT release. Phosphoramidon (PAN, 10 microM) 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 microM), enhanced both BN and NM-C inhibition of 3H-5-HT release. Bestatin (BST, 10 microM) 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 mechanism; 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 selectively augment or reduce pharmacologic activity of BN-like peptides upon CNS administration.
Saporito
M S
MS
Department of Pharmacology and Toxicology, Philadelphia College of Pharmacy and Science, PA 19104.
Warwick
R O
RO
D000595:Amino Acid Sequence; D000626:Aminopeptidases / Q000037:antagonists & inhibitors; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D001414:Bacitracin / Q000494:pharmacology; D001839:Bombesin / Q000494:pharmacology*; D004347:Drug Interactions; D004656:Enalapril / Q000031:analogs & derivatives / Q000494:pharmacology; D015773:Enalaprilat; D006020:Glycopeptides / Q000494:pharmacology; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism*; D007930:Leucine / Q000031:analogs & derivatives / Q000494:pharmacology; D008297:Male; D008969:Molecular Sequence Data; D015287:Neurokinin B / Q000031:analogs & derivatives* / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology*; D011480:Protease Inhibitors / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000378:metabolism*
D000806:Angiotensin-Converting Enzyme Inhibitors; D006020:Glycopeptides; D010446:Peptide Fragments; D011480:Protease Inhibitors; D001414:Bacitracin; D012701:Serotonin; D004656:Enalapril; C040794:neuromedin C; D015287:Neurokinin B; C038393:neuromedin B; D000626:Aminopeptidases; D007930:Leucine; D015773:Enalaprilat; C012211:ubenimex; D001839:Bombesin; C008890:phosphoramidon