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Biomedical subjects

M Lis

Publications and source records attributed to M Lis.

At least 55 records · Page 3Linked to original sources
PubMed1978

Lipotropin, melanotropin and endorphin: in vivo catabolism and entry into cerebrospinal fluid.

Anesthetized rabbits were given intravenous injections of either beta-lipotropin (beta-LPH), beta-melanotropin (beta-MSH) or beta-endorphin. The postinjection concentrations of these peptides in plasma and cerebrospinal fluid (CSF) were measured by radioimmunoassay (RIA). The plasma disappearance half-times were 13.7 min for beta-LPH, 5.1 min for beta-MSH, and 4.8 min for beta-endorphin. Circulating beta-LPH is cleaved to peptides tentatively identified as gamma-LPH and beta-endorphin. Each of these peptides appeared in the CSF within 2 min postinjection. The maximum CSF to plasma ratios were 0.08 for beta-LPH, 1.48 for beta-MSH,and 0.23 for beta-endorphin.

Animals↗
PubMed1978

Development of hyperlipidemia associated with increased lipolytic response of isolated adipose tissue cells following prolonged stimulation by an ectopic pituitary tumor.

Implantation of MtT-F4 tumor, a mammotropic tumor that secretes large quantities of ACTH, GH and prolactin, into male Fisher rats induced the development of hyperlipidemia. Free fatty acid, triglyceride and cholesterol levels in the plasma were significantly increased at 31 days after tumor implantation. Blood glucose and glycerol levels remained normal, while uric acid concentration in the blood was significantly decreased. The lipolytic response of isolated adipose tissue cells to ACTH was significantly higher in cells derived from rats bearing an MtT-F4 tumor for 31 days than from their corresponding controls. However, the activity of adenylate cyclase in fat cells stimulated with ACTH was not significantly higher in cells derived from tumor bearing rats than in cells from control rats.

Adenylyl Cyclases↗
PubMed1978

Biosynthesis of beta-endorphin from beta-lipotropin and a larger molecular weight precursor in rat pars intermedia.

When isolated rat pars intermedia cells were incubated for 10 min with radioactive amino acids, one major labeled protein with a molecular weight of 30,000 +/- 1500 was extracted. This protein was shown to contain in its sequence the antigenic determinants for corticotropin and beta-melanotropin by immunoprecipitation. When the radioactivity incorporated into this large molecular weight protein during the first 10 min was chased by a further incubation in presence of an excess of unlabeled amino acid, the initial protein was degraded into several smaller peptides including beta-endorphin and beta-lipotropin. Another 18,000-dalton peptide was also observed and was tentatively identified as a large molecular form of corticotropin. From the kinetics of the maturation of the initial precursor, it is concluded that the initial cleavage of the 30,000-dalton peptide gives rise to beta-lipotropin and the 18,000-dalton form of corticotropin. beta-Lipotropin is subsequently cleaved to form beta-endorphin.

Adrenocorticotropic Hormone↗
PubMed1978

In vitro biosynthesis and chemical characterization of beta-lipotropin, gamma-lipotropin, and beta-endorphin in rat pars intermedia.

Three 3-hr incubations of pars intermedia cells from 40 rat pituitaries with [35S]methionine, [3H]lysine, and [3H]leucine sufficed for the identification and chemical characterization of biosynthesized beta-lipotropin, gamma-lipotropin, and beta-endorphin. From the molecular weight, migration on polyacrylamide gels, and sequence Met5, Lys9, Leu14,17, rat beta-endorphin was shown to be identical to its sheep homologue and no trace of Leu5 beta-endorphin could be detected. Rat beta-lipotropin differs from that of sheep in its elution properties on CM-cellulose, and its sequence shows Leu2,10,14, Lys20. Rat gamma-lipotropin shows the same NH2-terminal sequence as beta-lipotropin and is again different from its sheep homologue. The identification of rat beta-lipotropin was confirmed by its selective cleavage into beta-endorphin after trypsin digestion of the citraconylated peptide, a property not observed with rat gamma-lipotropin.

Amino Acid Sequence↗
PubMed1978

Immunoreactive beta-endorphin in the rat mammotropic transplantable tumor (MtT-F4).

Raised levels of what appeared to be beta-lipotropin (beta-LPH), beta-melanotropic hormone, and beta-endorphin were detected by radioimmunoassay in the plasma of rats bearing the mammotropic transplantable pituitary tumor MtT-F4. The immunoreactivity to anti-beta-endorphin in the assay was displayed by a substance with the molecular weight of beta-LPH, as determined by gel filtration. Isolated cells of MtT-F4 tumor incubated in vitro released immunoreactive beta-LPH and beta-endorphin, with the expected molecular weights, into the incubation medium. These results suggest that the pituitary transplantable rat tumor MtT-F4 secretes peptides structurally related to beta-LPH.

Adrenocorticotropic Hormone↗
PubMed1977

A betaLPH precursor model: recent developments concerning morphine-like substances.

In summary, the pituitary glands from at least four species contain betaLPH and and beta endorphins. We have shown that in slices of whole pituitaries betaLPH is actively biosynthesized and transformed into gammaLPH, thus releasing the COOH-terminus portion 61--91, which is now known as beta-endorphin. Newly radioactive biosynthesized beta-endorphin has been clearly and definitely identified. The release of betaMSH and possibly of beta-endorphin could well be under the control of CRF. The intermediate lobe of the pituitary seems to be the tissue that contains most of betaLPH and beta-endorphin, although these are also present in the anterior lobe. We have recently demonstrated its presence in human glands and the structure is completely identical to the COOH-fragment 61--91 of human betaLPH. Thus far, these morphine-like peptides seem not to cross the blood-brain barrier in rats; it is conceivable (neurophysiologists will need to look into it) that an upward circulatory process could bring beta-endorphin into the brain where it is concentrated in different regions as either native or degraded products both of which have similar activities. Until somebody shows that betaLPH and beta-endorphin are actively biosynthesized in other tissues, one can only assume that the pituitary gland is the primary source of the endogenous opiate substance(s) and that betaLPH is its or their biologic precursor. We have worked on the proposed biosynthetic model for many years and we are continuing because all of the experiments, except one from another laboratory, 38indicate that we are moving slowly toward its confirmation. Thus far, there is no reason to believe the contrary, and we are following in some ways Konrad Lorenz's maxim, which appeared in his book Die Acht Todsunden Der Zivilisierten Menscheit, published in French in 1973: "Une bonne hypothése de travail gagne en vraisemblance lorsque, au cours de longues années de recherches, nulle donnée n'est venue la contredire." The major conclusion of our most recent studies on the biosynthesis of betaLPH and its related peptides have led us to the first in vitro biosynthesis of an endogenous morphine-like substance. This constitutes a major step in the comprehension of this exciting new field.

Amino Acid Sequence↗
PubMed1977

Evidence for topographical analogy between methionine-enkephalin and morphine derivatives.

Analogues of the endogenous opiate-receptor ligand [5-methionine]enkephalin (H-Tyr-Gly-Gly-Phe-Met-OH) were designed and synthesized for the purpose of testing the proposed similarity in spatial structure between this peptide and morphine derivatives. In the bioassay (inhibition of electrically induced contractions of the mouse vas deferens) [1-O-methyltyrosine,5-methionine]enkephalin, [1-N-methyltyrosine,5-methionine]enkephalin, [4-tryptophan,5-methionine]enkephalin, and [5-methionine sulfoxide]enkephalin possess, respectively, 0.4, 21, 27, and 67% activity of [5-methionine]enkephalin. These morphinomimetic activities correlate well with the opiate receptor affinities determined by displacement of [3H]naloxone in a guinea pig brain membrane preparation. The effects of O-methylation of the tyrosine residue and N-methylation of the terminal amino group on biological activity and receptor affinity support the hypothesis that the latter two moieties in the peptide correspond to the phenol group and the tertiary nitrogen, respectively, in morphine. Determination of the efficiency of energy transfer from tyrosine in position 1 to tryptophan in position 4 in [4-tryptophan,5-methionine]enkephalin from both tyrosine fluorescence quenching and relative enhancement of tryptophan fluorescence by means of a modified procedure permitted the calculation of an average intramolecular tyrosine-tryptophan separation of 10.0 +/- 1.1 A. Inspection of CPK models showed excellent agreement between this value and both the intrafluorophore distance in the 4 leads to 1 and 5 leads to 2 hydrogen bonded betaI-bend models of [4-tryptophan,5-methionine]enkephalin (9-11 A) and the phenol-phenyl separation in the potent morphine derivative 7alpha-(1(R)-hydroxy-1-methyl-3-phenylpropyl)-6,14-endo-ethenotetrahydrooripavine (8-10.5 A). The ensemble of these findings suggests an analogous topography for [5-methionine]enkephalin and morphine-oripavine derivatives.

Animals↗
PubMed1977

In vitro biosynthesis of beta-endorphin, gamma-lipoprotein, and beta-lipotropin by the pars intermedia of beef pituitary glands.

Labeled amino acids were incorporated with proteins during incubations of isolated cells from the pars intermedia of beef pituitary glands. After 3 hr of incubation with methionine and [3H]lysine, approximately equivalent amounts of labeled gamma-lipotropin and beta-endorphins were isolated. They were found to be major synthesis products of the pars intermedia. In contrast, very little labeled beta-lipotropin was recovered. Another major synthesis product of the pars intermedia was also purified. Its partial amino acid sequence and molecular weight were determined and it was concluded that this peptide cannot be identified as any known pituitary hormone or protein fragment.

Amino Acid Sequence↗
PubMed1977

In vitro biosynthesis of beta-endorphin in pituitary glands.

beta-Endorphin is a 31 amino acid polypeptide isolated from the pituitary gland of different species of animals. It has strong morphine-like activity. It is formed of amino acid residues 61-91 of beta-lipotropin. Speculation has arisen whether it is biosynthesized in situ or transformed after secretion of beta-lipotropin. The present in vitro studies show that it is found as beta-endorphin in bovine pituitary slices incubated with radioactive amino acid precursor [35S]methionine. Chemical characterization and microsequencing of the newly biosynthesized material proves its identity with isolated unlabeled beta-endorphin and shows that it has a methionine residue at its fifth position, as expected.

Amino Acids↗