Aplysia peptide neurotransmitters beta-bag cell peptide, Phe-Met-Arg-Phe-amide, and small cardioexcitatory peptide B are rapidly degraded by a leucine aminopeptidase-like activity in hemolymph.
We have been investigating the role of proteolytic enzymes in the inactivation of peptide neurotransmitters in the marine snail Aplysia. Previous studies (Squire, C. R., Talebian, M., Menon, J. G., Dekruyff, S. D., Lee, T. D., Shively, J. E., and Rothman, B. S. (1991) J. Biol. Chem. 266, 22355-22363) showed that neuroactive fragments of the neurotransmitter alpha-bag cell peptide (alpha-BCP) were rapidly degraded (t1/2 = 0.5-2.7 min) in plasma, hemolymph that had been cleared by centrifugation. Degradation was caused by one or more enzymes resembling mammalian leucine amino-peptidase (LAP, EC 3.4.11.1). In this report we show that three other Aplysia peptide neurotransmitters, beta-BCP(1-5) (Arg-Leu-Arg-Phe-His), FMRFa (Phe-Met-Arg-Phe-amide), and SCPB(1-9) (Met-Asn-Tyr-Leu-Ala-Phe-Pro-Arg-Met-amide) are rapidly degraded (t1/2 = 0.3-2.4 min) in plasma by apparently the same LAP-like enzyme(s). Our findings strongly suggest that the LAP-like enzyme(s), by means of its broad substrate specificity and access to the extracellular spaces of the nervous system in vivo, plays a significant role in the inactivation of many Aplysia peptide neurotransmitters, and they raise the possibility that proteolytic enzymes in the extracellular fluid contribute significantly to the inactivation of peptide neurotransmitters in other animal species.
Rothman
B S
BS
Department of Biology, San Francisco State University, California 94132.
Dekruyff
S
S
Talebian
M
M
Menon
J G
JG
Squire
C R
CR
Yeh
C H
CH
Lee
T D
TD
D000595:Amino Acid Sequence; D000818:Animals; D001048:Aplysia / Q000201:enzymology*; D006458:Hemolymph / Q000201:enzymology*; D007447:Invertebrate Hormones / Q000378:metabolism*; D007931:Leucyl Aminopeptidase / Q000378:metabolism*; D013058:Mass Spectrometry; D008969:Molecular Sequence Data; D009479:Neuropeptides / Q000378:metabolism*; D010446:Peptide Fragments / Q000302:isolation & purification; D013379:Substrate Specificity
D007447:Invertebrate Hormones; D009479:Neuropeptides; D010446:Peptide Fragments; C026880:egg-laying hormone, Mollusca; C041307:small cardioactive peptide B; D007931:Leucyl Aminopeptidase