SOMATOSTATIN BIOSYNTHESIS AND SECRETION

  • Roos, Bernard A (PI)

Project: Research project

Project Details

Description

The objective of the proposed studies is to ascertain the separate and combined
regulatory effects of endocrine and neural factors on the production and
metabolism of calcitonin (CT) and its biosynthetic precursors--procalcitonin
(proCT) and a putative prepolcalcitonin (preproCT). For these studies we will
employ in vitro preparations of functional C-cells, including organ cultures,
suspension cultures, and long-lived monolayer cultures. Our preliminary
investigations have shown these C-cell preparations to be exceptionally well
suited for regulatory studies of both production and secretion of CT. For
instance, we have noted regulatory actions and interactions of enteric
polypeptide hormones and vitamin D metabolites and adrenergic and cholinergic
agonists on CT production and secretion. Our studies will characterize the
separate and combined effects of many neural and endocrine factors on CT
secretion and production. We will determine the acute and/or chronic effects of
individual and combined regulatory factors on the rates of synthesis, of
cleavage, and of degradation of CT, proCT, and preproCT. Relative changes in
the rates of these processes will be studied by pulse, pulse-chase, and
double-label radioisotopic techniques. Immunoextracted radiolabeled CT moieties
chromatography. Regulatory effects on the concentrations of specific CT
moieties will be assessed by radioimmunoassay. Effects on the rates of
production, cleavage, and/or degradation of CT, proCT, and preproCT will be
assessed by incorporation and by decay of radioactivity in specific CT moieties. Understanding the individual and combined regulatory effects of endocrine and
neural factors on the rates of synthesis and proteolysis of specific CT moieties
will illuminate the metabolic basis for the multifactorial regulation of
polypeptide biosynthesis and secretion in eukaryotic cells.
StatusFinished
Effective start/end date1/1/8512/31/85

Funding

  • National Institutes of Health

ASJC

  • Medicine(all)

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