Search PubMed⌕ Search

Biomedical subjects

R V Lewis

Publications and source records attributed to R V Lewis.

At least 91 records · Page 5Linked to original sources
PubMed1983

Biosynthesis of the enkephalins and enkephalin-containing polypeptides.

The biochemical characterization of the enkephalins and the enkephalin-containing polypeptides and their biosynthesis has reached an advanced state. From the structural data showing great similarities between human and beef proenkephalin there is strong evidence for physiological roles for some of the extended enkephalins and for at least two of the ECPs. If, like the different hormones contained within proopiocortin, the different ECPs in proenkephalin perform different coordinate functions, their cosecretion with the catecholamines from the adrenal gland suggests that these functions play a role in the response to stress. It appears that proenkephalin represents another multi-hormone precursor, like proopiocortin, that is processed by proteolysis to yield a variety of peptides active in both the endocrine and nervous systems. The research effort must now turn toward resolving the nature of the physiologic functions these peptides perform.

Amino Acid Sequence↗
PubMed1982

Adrenal opioid proteins of 8600 and 12,600 daltons: intermediates in proenkephalin processing.

[Met]Enkephalin-containing proteins of 8600 and 12,600 daltons have been isolated from acid extracts of bovine adrenal medulla and purified to homogeneity, and their sequences have been determined by a combination of automated Edman degradation, tryptic mapping, and enzymatic time-course hydrolysis. The 8600-dalton protein contains one copy of the [Met]enkephalin sequence at the COOH terminus and the 12,600-dalton protein contains three copies of [Met]enkephalin, of which two are internal and the third is at the COOH terminus. They possess identical NH2-terminal amino acid sequences, suggesting that the 8600-dalton protein is derived from the 12,600-dalton protein by intracellular proteolytic processing. This is supported by results from tryptic maps of both proteins. Furthermore, chemical analysis of the tryptic peptides obtained from the 12,600-dalton protein indicates that it also contains the amino acid sequence that corresponds to a previously characterized enkephalin-containing polypeptide of 3800 daltons (peptide F) [Jones et al. (1980) Arch. Biochem. Biophys. 204, 392-395]. All three polypeptides appear to be intermediates in posttranslational processing of a still larger polyenkephalin precursor molecule, proenkephalin, and part of a biosynthetic pathway leading to smaller enkephalin-containing polypeptides and free enkephalins.

Adrenal Medulla↗
PubMed1982

An 18,200-dalton adrenal protein that contains four [Met]enkephalin sequences.

An 18,200-dalton adrenal enkephalin-containing polypeptide was purified to homogeneity and shown to contain four internal [Met]enkephalin sequences. Protein sequence analysis and mapping of trypsin-derived peptides demonstrated that the previously described 12,600-dalton and 5,300-dalton adrenal enkephalin-containing polypeptides compose the amino-terminal and carboxyl-terminal sequences, respectively, of this larger protein. They are linked by two basic amino acid residues to form the entire sequence of the 18,200-dalton protein. This protein is the largest enkephalin-containing polypeptide yet isolated from beef adrenal medulla and serves as the precursor for several other previously characterized adrenal enkephalin-containing proteins and peptides.

Adrenal Medulla↗
PubMed1982

Enkephalin biosynthesis in the adrenal medulla.

Although the number of enkephalin-containing polypeptides (ECP's) from bovine adrenal chromaffin granules have been isolated and sequenced the complete sequence of the translation product has not been determined. Preliminary data from cDNA suggests a 1500 mRNA is the precursor mRNA. Continuation of that line of research to clone the cDNA should provide the total precursor amino acid sequence. Data obtained from ovine chromaffin granules indicates that the ECP's from the species are very similar to those in bovine granules. If this is extended to other species it would appear that some of the ECP's may serve a role beyond that of an enkephalin precursor. In an analogy to pro-opiocortin the "proenkephalin" also may contain multiple hormone sequences. The sequences determined thus far imply trypsin-like enzymes and a carboxy-peptidase B are used to cleave the precursor. We have determined that both types of enzymes are indeed present in chromaffin granules and further studies of these enzymes will provide information of how the precursor cleavages are regulated.

Adrenal Medulla↗
PubMed1981

The solubility of bovine lens crystallins.

Apparent thermodynamic parameters for the process of solubilization of the five major classes of bovine lens crystallins have been determined by the polyethylene glycol solubility method. Although each purified crystallin fraction displays significant structural heterogeneity as analyzed by high performance liquid chromatography, they behave as homogeneous proteins by the criteria of solubility. Using experimentally determined values for the apparent enthalpy and entropy of solution and the effects of a variety of low molecular weight solutes on crystallin solubility, the five classes can be arranged in order of the polarity of their solid phase intermolecular contacts as follows: gamma, high molecular weight beta greater than low molecular weight beta greater than high molecular weight alpha greater than alpha. Since alpha-crystallin is the major component of the insoluble material in bovine cataract, we suggest that cataract formation may be related to the intrinsic solubility and polarity of the lens crystallins.

Animals↗
PubMed1981

Marked increases in large enkephalin-containing polypeptides in the rat adrenal gland following denervation.

When rat adrenal glands are denervated, large increases in the amounts of enkephalin and enkephalin-containing polypeptides appear. In the normal gland, only trace amounts occur. One of the larger polypeptides (approximately 22,000 daltons) increases rapidly and by 48 hr following denervation, attains 20 times its original level. At this time, the levels of free enkephalins are essentially unchanged. By 96 hr, the 22,000-dalton polypeptide begins to decrease as free enkephalins and intermediate-sized enkephalin-containing polypeptides increase. This series of events is consistent with a precursor (22,000-dalton polypeptide)/product (enkephalin) relationship.

Adrenal Glands↗
PubMed1980

An about 50,000-dalton protein in adrenal medulla: a common precursor of [Met]- and [Leu]enkephalin.

A protein that may be an enkephalin precursor has been identified in extracts of bovine adrenal medulla. This protein (about 50,000 daltons) appears to contain seven copies of [Met]enkephalin and one copy of [Leu]enkephalin. Digestion with trypsin and carboxypeptidase B yields [Met]enkephalin and [Leu]enkephalin in a ratio of almost 7 to 1. The enkephalins were identified by chromatography and by their binding to opiate receptors. Some characteristics of several other adrenal peptides that may serve as intermediates in the biosynthesis of the enkephalins are presented.

Adrenal Medulla↗
PubMed1980

Studies with [35S]methionine indicate that the 22,000-dalton [Met]enkephalin-containing protein in chromaffin cells is a precursor of [Met]enkephalin.

It has been shown that [35S]methionine is incorporated into the [Met]enkephalin sequences of a 22,000-dalton enkephalin-containing protein in the adrenal medulla. Pulse-chase experiments indicate that label is incorporated into the large polypeptide before it appears in free [Met]enkephalin and a smaller [Met]enkephalin-containing peptide. These findings provide direct evidence of a precursor-product relationship of these structurally related polypeptides.

Adrenal Medulla↗
PubMed1980

Release of enkephalins and enkephalin-containing polypeptides from perfused beef adrenal glands.

Enkephalins and enkephalin-containing polypeptides were released from perfused bovine adrenal glands by nicotine and Ba2+, agents that release catecholamines. All the enkephalin-containing polypeptides that are normally found in the adrenal medulla were released by the two secretagogues in approximately the same proportions as are present in adrenal chromaffin granules.

Adrenal Glands↗
PubMed1980

Probable precursors of [Leu]enkephalin and [Met]enkephalin in adrenal medulla: peptides of 3-5 kilodaltons.

Adrenal chromaffin granules contain at least 10 peptides, ranging in size from 3 to 5 kilodaltons, that yield, upon digestion with trypsin, peptides that show specific binding to opiate receptors. All are distinctly different from beta-endorphin. Two of these peptides have been purified to homogeneity and subjected to chemical analysis. One is apparently a [Met]enkephalin precursor containing two copies of the [Met]enkephalin sequence. The other peptide contains both [Leu]enkephalin and [Met]enkephalin sequences and is presumably a common precursor of the two forms of enkephalin.

Adrenal Medulla↗
PubMed1980

Enkephalin biosynthetic pathway: proteins of 8000 and 14,000 daltons in bovine adrenal medulla.

Two [Met]enkephalin-containing polypeptides have been purified from extracts of bovine and adrenal chromaffin granules. One is 8000 daltons in size and contains the enkephalin sequence at the carboxy terminus. The other (14,000 daltons) has two internal enkephalin sequences and a third sequence at the carboxy terminus. All of these sequences can be released by trypsin, indicating a possible enkephalin precursor role for the polypeptides.

Adrenal Medulla↗
PubMed1980

Analgesic activity of the naturally occurring heptapeptide [Met]enkephalin-Arg6-Phe7.

[Met]Enkephalin-Arg6-Phe7 is an opiate-like peptide normally found in the the adrenal gland and brain that has analgesic (antinociceptive) activity when administered directly into the cerebral ventricles of mice. On a molar basis, [Met]-enkephalin-Arg6-Phe7, with a median effective dose (ED50) of 38.5 nmol/mouse, is 8 times more potent than [Met]enkephalin. As with [Met]enkephalin, analgesic activity is blocked by naloxone and intravenous administration does not produce characteristic opiate effects in tests for analgesic, antidiuretic, or antidiarrheal activity. These findings suggest that [Met]enkephalin-Arg6-Phe7 may be at least as important as the enkephalins in the postulated enkephalin system mediating pain and analgesia.

Analgesics↗