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Manipulation of Neuropeptide Biosynthesis through the Expression of Antisense RNA for Peptidylglycine α-Amidating Monooxygenase

1991; Oxford University Press; Volume: 5; Issue: 2 Linguagem: Inglês

10.1210/mend-5-2-187

1944-9917

Richard E. Mains, Brian T. Bloomquist, Betty Eipper,

Adipose Tissue and Metabolism

Stable cell lines with significantly elevated or diminished levels of a key neuropeptide processing enzyme, peptidylglycine alpha-amidating monooxygenase (PAM), were generated by transfection of a mouse pituitary cell line with expression vectors containing PAM cDNA in the sense or antisense orientation. By evaluating the ability of these cell lines to alpha-amidate endogenous neuropeptides, a rate-limiting role for PAM in neuropeptide alpha-amidation was demonstrated. Overexpression of either the full-length PAM precursor with its trans-membrane domain or a soluble protein containing only the monooxygenase domain of PAM led to increased alpha-amidation of endogenous neuropeptides. Overexpression of the full-length PAM led to an unexpected decrease in the endoproteolytic processing of endogenous prohormone; conversely, underexpression of PAM led to significantly enhanced endoproteolytic processing of endogenous prohormone. These data suggest that PAM may have additional functions in peptide processing.