Opioid peptides are synthesized in the form of large precursors, which contain the information for more than one biologically active peptide. Using recombinant DNA technology, three opioid precursors have been sequenced: pro-opiomelanocortin (POMC), proenkephalin and prodynorphin. Analysis of the structures of these three precursors and their corresponding genes show striking similarities suggesting a common evolutionary mechanism. Regulation of POMC gene expression has been analyzed in different rat tissues. Detection of POMC mRNA in brain tissues supports the hypothesis that ACTH and endorphin peptides are synthesized in these tissues. Quantitation of POMC mRNA levels in pituitaries of rats subjected to adrenalectomy and glucocorticoid treatment shows that the feedback effect of the glucocorticoids occurs at the level of the rate of transcription of POMC mRNA.

Adrenalectomy↗

PubMedDate not supplied

Polymorphism and absence of Leu-enkephalin sequences in proenkephalin genes in Xenopus laevis.

The structures of the genes coding for the opioid peptide precursors proopiomelanocortin, proenkephalin (proenkephalin A) and prodynorphin (proenkephalin B), are known for some mammalian species. To gain insight into the evolutionary history of these precursors, we have examined the proenkephalin gene in the South African clawed toad, Xenopus laevis, which diverged from the principal line of vertebrate evolution some 350 Myr ago. The human proenkephalin gene consists of four exons, of which the main exon (exon IV) contains all known biologically active peptides--six Met-enkephalin sequences and one Leu-enkephalin sequence. We report here the primary structures of the putative main exons of two proenkephalin genes in X. laevis, each of which codes for seven Met-enkephalin sequences but no Leu-enkephalin, indicating that Met-enkephalin preceded Leu-enkephalin in the evolution of the proenkephalin gene. The organization of the main exons of the toad genes is remarkably similar to that of the human gene and conserved regions provide evidence for functionally significant structures. We also detect a polymorphism in one of the toad proenkephalin genes, mapping 1.5 kilobases (kb) 5' of the main exon; it is caused by an insertion/deletion of a 1-kb repetitive sequence which has the characteristics of a transposable element.

Amino Acid Sequence↗

PubMedDate not supplied

Bovine chromogranin A sequence and distribution of its messenger RNA in endocrine tissues.

Chromogranin A is contained in storage vesicles of chromaffin cells of the adrenal medulla and released with catecholamines when the splanchnic nerve is stimulated. Chromogranin A is similar to secretory protein I (SP-I), a major secreted protein of the parathyroid. Chromogranin A/SP-I immunoreactivity is abundant in endocrine cells that secrete peptide hormones from storage vesicles. Chromogranins may act in neuroendocrine secretion by binding intravesicular calcium. Serum levels of chromogranin are raised in hypertension and endocrine neoplasia. We report here the isolation and sequencing of a cDNA encoding bovine chromogranin A, providing the first complete primary structure of a chromogranin protein. Chromogranin A is a highly acidic protein with an apparent relative molecular mass (Mr) of 75,000 on SDS-PAGE, but an actual Mr of 48,000. Adrenal medulla, brain, pituitary and parathyroid are all sites of synthesis of chromogranin A. The primary structure of chromogranin A, and the presence of chromogranin mRNA in the parathyroid, indicate that chromogranin A and SP-I are identical.

Adrenal Medulla↗