Production of a novel neuropeptide encoded by the calcitonin gene via tissue-specific RNA processing

  title={Production of a novel neuropeptide encoded by the calcitonin gene via tissue-specific RNA processing},
  author={Michael G. Rosenfeld and J J Mermod and Susan G. Amara and Larry W. Swanson and Paul E Sawchenko and Jean Edouard Frederic Rivier and Wylie W. Vale and Ronald M. Evans},
Alternative processing of the RNA transcribed from the calcitonin gene appears to result in the production of a messenger RNA in neural tissue distinct from that in thyroidal ‘C’ cells. The thyroid mRNA encodes a precursor to the hormone calcitonin whereas that in neural tissues generates a novel neuropeptide, referred to as calcitonin gene-related peptide (CGRP). The distribution of CGRP-producing cells and pathways in the brain and other tissues suggests functions for the peptide in… 

Calcitonin Gene—Related Peptide: A Neuropeptide Generated as a Consequence of Tissue‐Specific, Developmentally Regulated Alternative RNA Processing Events

The distribution of C GRP mRNA and peptide in the brain and other tissues and initial studies of biological actions of the synthetic peptide suggest functions for CGRP at the neuromuscular junction in modulation of cardiovascular homeostasis5 and in pain perception.

Biosynthesis of the Tachykinins and Somatostatin

The expression of a single neuropeptide gene may, in different tissues, give rise to alternative patterns of biologically active peptides, the best known example is pro-opiomelanocortin, the common precursor to adrenocorticotrophic hormone, the melanocyte-stimulating hormone and the endorphin family of opioid peptides.

Stimulation of noradrenergic sympathetic outflow by calcitonin gene-related peptide

It is reported here that CGRP acts in the central nervous system to stimulate selectively noradrenergic sympathetic outflow and is identified immunocytochemically throughout the central and peripheral nervous systems.

Alternative RNA processing: determining neuronal phenotype.

The distribution of CGRP in the central and peripheral nervous system and in endocrine and other organ systems suggests potential functions in nociception, ingestive behavior, cardiovascular homeostasis, and mineral metabolism.

Expression in brain of a messenger RNA encoding a novel neuropeptide homologous to calcitonin gene-related peptide.

As a consequence of alternative RNA processing events, a single rat gene can generate messenger RNA's (mRNA's) encoding either calcitonin or a neuropeptide referred to as alpha-type calcitonin

Release of the predicted calcitonin gene-related peptide from cultured rat trigeminal ganglion cells

It is reported here that immunoreactive CGRP is spontaneously released by cultured trigeminal ganglion cells and that secretion is stimulated by incubation in high potassium medium in a calcium-dependent fashion.



Calcitonin messenger RNA encodes multiple polypeptides in a single precursor.

The location of glycine next to the carboxyl terminal prolinamide of calcitonin is consistent with indications that glycine is required for the enzymatic amidation of proline to the prolinamines in cellular biosynthesis.

Calcitonin mRNA polymorphism: peptide switching associated with alternative RNA splicing events.

  • M. RosenfeldC. Lin R. Evans
  • Biology
    Proceedings of the National Academy of Sciences of the United States of America
  • 1982
Evidence is presented which supports a model proposing that differential RNA splicing events may be used in expression of genes of the endocrine system to generate alternative polypeptide hormones.

Altered expression of the calcitonin gene associated with RNA polymorphism

It is reported here that the conversion from a ’high’ to a ‘low’ calcitonin producing state is associated with specific modifications of the calcitonIn mRNA synthetic pathway and a consequence of these changes seems to be the production of a new cytoplasmic mRNA.

Characterization of rat calcitonin mRNA.

A chimeric plasmic containing cDNA complementary to rat calcitonin mRNA has been constructed and partial sequence analysis shows that the insert contains a nucleotide sequence encoding the complete amino acid sequence of calciton in a manner analogous to that of other small polypeptide hormones.

Absence of detectable calcitonin synthesis in the pituitary using cloned complementary deoxyribonucleic acid probes.

It is concluded that a mRNA homologous in sequence to that encoding rat thyroidal CT is not synthesized in the pituitary gland, and CT biosynthesis in rat pituitaries using specific and sensitive hybridization assays which used a cloned CT complementary DNA (cDNA) to detect CT mRNAs.

Immunoreactive human calcitonin-like molecule in the nervous systems of protochordates and a cyclostome, Myxine.

A molecule very closely resembling human calcitonin immunologically and chromatographically was extracted from the nervous systems of several protochordates and a cyclostome, Myxine, suggesting they have some function in the nervous system of these species and that the bone-regulating function of the calcitonins may have arisen much later in the vertebrates.

Distribution of beta-endorphin immunoreactivity in normal human pituitary.

This immunoperoxidase study demonstrates a similar distribution for beta-endorphin and ACTH immunoreactivity in human pituitary; however, the two peptides are not necessarily present in the same cells at all times; it appears that the immunoreactive calcitonin in human Pituitary differs from that in thyroid C cells.