Structure-activity relationship of the neurotransmitter alpha-bag cell peptide on Aplysia LUQ neurons: implications regarding its inactivation in the extracellular space.

Alpha-bag cell peptide alpha-BCP (Ala-Pro-Arg-Leu-Arg-Phe-Tyr-Ser-Leu)] is a neurotransmitter that mediates bag cell-induced inhibition of left-upper-quadrant (LUQ) neurons L2, L3, L4, and L6 in the abdominal ganglion of Aplysia. Our recent biochemical studies have shown that alpha-BCP1-9] is cleaved into alpha-BCP1-2], 3-9], 1-5], 6-9], and 7-9] by a combination of three distinct peptidase activities located within the extracellular spaces of the CNS: A diaminopeptidase-IV (DAP-IV)-like enzyme cleaves alpha-BCP1-9] at the 2-3 peptide bond; a neutral metalloendopeptidase (NEP)-like enzyme cleaves either alpha-BCP1-9] or alpha-BCP3-9] at the 5-6 bond; an aminopeptidase M-II (APM-II)-like enzyme cleaves alpha-BCP6-9] at the 6-7 bond, but cleaves neither alpha-BCP1-9], nor the other ganglionic peptidase products. To further understand the manner in which alpha-BCP is inactivated after release, that is loses its electrophysiological activity, we studied its structure-activity relationship by recording intracellularly from LUQ neurons in isolated abdominal ganglia that were arterially perfused with peptides dissolved in artificial sea water. The effects of alpha-BCP1-9] and 15 of its fragments (1-8], 1-7], 1-6], 1-5], 2-9], 3-9], 3-8], 6-9], 7-9], 8-9], 6-7], 6-8], 1-2], Phe, Tyr) indicated that the sequence Phe6-Tyr7 was both necessary and sufficient to produce LUQ inhibitory activity.(ABSTRACT TRUNCATED AT 250 WORDS)