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L H Lazarus

Publications and source records attributed to L H Lazarus.

At least 73 records · Page 4Linked to original sources
PubMed1987

Structure-activity relationship of dermorphin on gastric secretion.

The amphibian skin heptapeptide dermorphin (DM) administered intracerebroventricularly to rats significantly reduces gastric secretion. Dermorphin and 19 DM homologs and analogs were tested for their effect on gastric volume, pH, H+ ion concentration, and gastric acid output. DM, DM N-terminal pentapeptide and tetrapeptide amides, [D-Met2]DM, [Sar4]DM, [Trp5]DM, [Phe5]DM, [Gly7]DM, [Ser(Bzl)7]DM, and deamidated-DM significantly (P less than 0.01) reduced gastric acid output 2 h after injection. These data provide evidence for the following conclusions on the effect of DM on gastric secretion: ability to inhibit gastric secretion depends on the presence of the D-isomer of Ala at position 2, since [L-Ala2]DM is inactive; the shortest sequence with significant bioactivity is DM N-terminal tetrapeptide amide; the single replacement of amino acid residues in DM elicits a wide range of activities, varying from full biological activity of [Gly7]DM to those analogs with a complete lack of activity, such as [Pro4]DM and [Gly6]DM; and 4) coupling of protective groups to amino and hydroxyl groups of DM results in a significant loss of activity.

Animals↗
PubMed1986

An immunoreactive peptide in milk contains bombesin-like bioactivity.

Parallel in vitro bioassays using rat uterus and guinea pig large intestine tissues specific for the bombesin family of peptides, demonstrated that the bombesin-like peptides present in bovine milk can produce a dose-related response similar to bombesin and litorin. The bioactivity of this type of milk peptide appeared to be approximately 20-50% as active as the amphibian peptides. These data support the proposal that a bombesin immunoreactive peptide in milk contains bombesin bioactivity.

Animals↗
PubMed1986

Physalaemin-like immunoreactive peptides from rabbit stomach.

Two physalaemin (PHY)-like immunoreactive peptides, designated PHLIPs, have been purified from extracts of rabbit stomach tissue. Fast atom bombardment/mass spectrometry (FAB/MS) indicated that the m/z values for the PHLIP protonated molecular ions were 867.419 and 796.4. FAB/tandem MS spectra, coupled with a knowledge of the amino acid composition and the aid of a computerized fragment-matching program, indicated the amino acid sequences to be: (formula; see text) The sequences of PHLIPs-7 and -8 were confirmed with synthetic peptides. The PHY-antiserum cross-reactivity of the PHLIPs reflects homology at amino acid residues 1, 3, 4 and 5 for the mammalian and amphibian residues.

Amino Acid Sequence↗
PubMed1985

Chemical and immunochemical characterisation of substance P-like immunoreactivity and physalaemin-like immunoreactivity in a carcinoid tumour.

Extracts of a carcinoid tumour, resected from the mid-portion of the ileum of a patient with no symptoms of endocrine disorder, were associated with a high concentration of substance P-like immunoreactivity. Using reverse-phase high performance liquid chromatography and antisera specifically directed against the C-terminal and N-terminal regions of substance P and against the N-terminal region of physalaemin, the following components were isolated and identified: substance P and its oxidised form, [pGlu5]substance P-(5-11) peptide and its oxidised form, and the oxidised form of physalaemin. The identity of tumour substance P with the undecapeptide was confirmed by amino acid analysis and high performance ion-exchange chromatography. In vitro incubation of tumour tissue from a lymph node metastasis from the same patient with [3H]leucine resulted in incorporation of radioactivity into newly synthesised substance P.

Carcinoid Tumor↗
PubMed1985

Central neuromodulation of gastric acid secretion by bombesin-like peptides.

The amphibian skin tetrapeptide bombesin shows potent action in reducing gastric acid secretion by intracerebral ventricular (ICV) administration in rats. In order to establish a relationship between this action and the amino acid composition of the bombesin-like peptides, most of the natural bombesin-like peptides and some synthetic analogues were tested on their ability to reduce gastric acid secretion by ICV administration. The amphibian peptides bombesin, its [Tyr4]-bombesin analogue, alytesin, ranatensin and litorin, and the mammalian peptide GRP significantly reduced gastric acid output 2 hr after peptide administration (p less than 0.01). The data support the following prerequisites for the maximal neuromodulatory role of bombesin-like peptides on gastric secretion: Trp is required at position 8; Gln and His are important at positions 7 and 12, respectively; Leu replacement by Phe, which occurs in the litorin subfamily, modifies the response; and unspecified amino acids or sequences are also involved in the N-terminal region of bombesin-like peptides. Synthetic analogues are currently being tested to confirm and extend these conclusions.

Amino Acid Sequence↗
PubMed1985

Active peptides from amphibian skin are also amphibian neuropeptides.

Immunohistochemical data on several newt brain areas showed a heterogeneous system of neuronal elements, immunopositive for antisera specifically directed to different antigenic determinants of tachykinin molecules. Acid extracts of newt brain areas were immunopositive for substance P with an antibody specific for the COOH-terminal (tachykinin determinant) and exhibits an elution profile by gel filtration characteristic to substance P. Bombesin-like immunoreactivity was demonstrable both by immunohistochemistry (fibers and cell bodies in forebrain and hypothalamic areas) and by radioimmunoassay, using an antiserum specific for the mid-region of the molecule. This immunoreactivity was separated into two peaks by gel filtration chromatography. Sauvagine-like material was detected by immunohistochemistry in newt hypothalamus as a loose preoptic cell system and as a thin fiber layer in the outer zone of the median eminence. Double staining procedures demonstrate that sauvagine and CRF are spatially closely related but separable in both the preoptic area and in the median eminence. This data on the presence of several amphibian skin peptides in the CNS of the newt suggests their possible role as neuropeptide.

Amphibian Proteins↗
PubMed1985

Evolutionary relationship between nonmammalian and mammalian peptides.

An hypothesis has been developed to rationalize the evolution of regulatory peptides. In order to account for critical relationships involving peptide regulators, their receptors, and peptide processing enzymes, the following generalizations will be supported: (1) peptides arose from protein precursors as proteolytic digestion by-products and acquired hormonal status during the course of natural selection; (2) initially, peptides served primarily nutritional roles, thereby permitting increased growth rates and reproductive advantages for recipient cells; (3) specific peptide sequences were conserved during evolution and were associated with biological activities which were essential for survival of species as divergent as unicellular organisms, amphibians, and mammals; and (4) regulatory peptides probably arose simultaneously with their membrane-oriented, macromolecular receptor sites. In support of the conservation of sequence information or function, or both, during evolutionary development, evidence has been obtained to indicate that peptide sequences which occur in two classes of amphibian peptides appear to be extensively conserved in mammals. Studies with an antiserum directed against the N-terminal sequence of amphibian physalaemin have permitted the recognition of a mammalian octapeptide which exhibits 80% homology with residues 1-5 in that region. Another study with an antiserum directed against the midregion (sequence 5-8) of amphibian bombesin has indicated the existence of milk peptides which mimic bombesin in several pharmacological bioassays. These studies indicate that radioimmunoassays can be powerful tools in facilitating recognition of peptide sequences conserved throughout evolution.

Amino Acid Sequence↗
PubMed1984

A bombesin immunoreactive peptide in milk.

Immunoreactivity to the amphibian peptide bombesin was found in instant nonfat dry milk (ca. 0.7 ng/ml) and in the whey of whole or skim bovine milk (ca. 1.2 ng/ml) even after ultracentrifugation. The soluble immunoreactivity was associated with a peptide exhibiting the following characteristics: (i) parallel displacement in an immunoassay using an antiserum recognizing bombesin amino acid residues 5-8; (ii) separation from both gastrin-releasing peptide and amphibian bombesin by gel filtration--the approximate Mr was 3,200; (iii) denaturation in urea, reduction by dithiothreitol, and acetylation by iodoacetamide had no effect on its elution profile by gel-filtration chromatography and the aggregation of added bombesin to milk proteins or peptides was not observed; (iv) reversed-phase HPLC separated milk immunoreactivity from gastrin-releasing peptide and bombesin; (v) digestion by trypsin yielded a smaller immunoreactive peptide fragment, whereas nearly all immunoreactivity was lost by treatment with alpha-chymotrypsin; and (vi) the level of immunoreactivity was unaffected by boiling. These data show that milk is an exogenous source of bombesin-like immunoreactivity, which may account for the increase of gastric acid and gastrointestinal hormone levels after the consumption of milk.

Animals↗
PubMed1984

Adrenocorticotropin radioimmunoassay: properties of antisera against synthetic ACTH(1-24) and its clinical application.

Two antisera against synthetic ACTH(1-24) developed in rabbit showed strikingly different affinities toward the ACTH molecule. Both antisera (A-6 and A-7) were highly specific for the COOH-terminal region of ACTH(1-24). Antisera A-6 recognized ACTH(1-39) poorly. Radioimmunoassays (RIAs) using these antisera permitted the rapid (less than or equal to 18 h) quantitation of ACTH(1-24) (A-6) or ACTH(1-39) (A-7) at picogram levels. ACTH levels were determined on silicic acid extracts of rat and human plasma samples by the RIA specific for mid-region of ACTH(1-39) (A-7) and compared with that obtained by an ACTH(34-39) (C-terminal) RIA. In nearly all cases the C-terminal/mid-region ACTH ratios were less than 1.0, indicating that C-terminus of ACTH is more readily degraded by tissue or blood peptidases than are internal sequences. A solid-phase immunoadsorbent RIA specific for the extreme COOH-terminus of ACTH(1-24) was developed by coupling antiserum (A-6) to Sepharose 4B. This assay exhibited the same specificity as the soluble antiserum, yet tolerated relatively high concentrations of protein. Although the assay was suitable for rapid quantitation of ACTH(1-24), a decrease in sensitivity was observed in comparison to a conventional assay.

Adrenocorticotropic Hormone↗
PubMed1983

Physalaemin: an amphibian tachykinin in human lung small-cell carcinoma.

Immunoreactivity to the amphibian peptide physalaemin was characterized from extracts of a human lung small-cell carcinoma by immunological, chemical, and pharmacological means. Tumor-related peptide cross-reacted with three antiserums to physalaemin to yield 1.1 to 1.6 nanomoles per gram of tissue. Physalaemin and tumor peptide had similar retention times on high-performance liquid chromatography after chemical and enzymic modifications that included pH changes, oxone oxidation, use of a hydrophilic ion-pairing reagent, and digestion with trypsin and pyroglutamate aminopeptidase. Both physalaemin and the tumor peptide produced a contractile response of isolated guinea pig ileum at threshold concentrations of approximately 100 to 150 picograms per milliliter. These data suggest that small-cell carcinoma of the lung contains a physalaemin-like peptide that has structural and biological homology to its amphibian counterpart.

Carcinoma, Small Cell↗
PubMed1982

Human lung small-cell carcinoma contains bombesin.

The presence of immunoreactive bombesin in a human lung small-cell carcinoma grown in nude mice was established by several criteria: (i) Radioimmunoassay of tissue extracts for bombesin revealed approximately 6.5 pmol/g of tissue; (ii) bombesin was found in 12-14% of the tumor cells by immunohistochemical localization; (iii) gel filtration of small-cell carcinoma extract on Sephadex G-75 and Bio-Gel P-4 gave only a single peak of immunoreactivity, which occurred at the elution volume of bombesin; and (iv) reverse-phase HPLC of acid-solubilized extracts separated the immunoreactive material into three discrete peaks, one of which eluted with a retention time identical to that of synthetic bombesin. The presence of bombesin may represent the ectopic expression of this peptide in small-cell carcinoma, because immunoreactive bombesin was found in human fetal and neonatal lung but apparently not in adult lung tissue [Wharton, J., Polak, J. M., Bloom, S. R., Ghatei, M. A., Solcia, E., Brown, M. R. & Pearse, A. G. E. (1978) Nature (London) 273, 769-770]. The immunoreactive bombesin previously found in mammalian tissues is considerably larger than amphibian bombesin; these data substantiate the presence of a mammalian form of bombesin in a human tumor that may have a structure similar to that of the amphibian peptide.

Animals↗
PubMed1982

A substance with immunoreactivity to the peptide physalaemin in mammalian respiratory tissue.

Physalaemin (Mr = 1284) is a potent undecapeptide from the skin of South American frogs. The amino acid sequence of the COOH-terminal region of this peptide is similar to that of substance P. An antiserum specific for the NH2-terminal sequence of physalaemin enabled the quantitation and localization of physalaemin-like immunoreactivity (PSLI) in mammalian tissues. PSLI is found in acid extracts of whole trachea from rat, rabbit, and guinea pig and in the tracheal mucosal layer in the dog, cow, and pig. The concentration determined by radioimmunoassay ranged from 1 to 15 ng/g dry weight of tissue, with rat trachea containing the highest amount. Gel filtration of an extract of rabbit trachea on Bio-Gel P-4 revealed a single peak of immunoreactivity that had an approximate Mr of 1700, similar to that detected in extracts of guinea pig and rabbit stomach. In contrast to amphibian physalaemin, mammalian PSLI 1) has a higher molecular weight, 2) is resistant to alpha-chymotrypsin or trypsin digestion, 3) elutes earlier from a C18 alkylsilane resin with increasing concentrations of methanol, and 4) can be separated from physalaemin by thin-layer chromatography. These data indicate that the mammalian PSLI is different in structure from the amphibian peptide.

Animals↗
PubMed1981

Application of a sequence-specific radioimmunoassay for the carboxyl-terminal region of corticotropin.

The carboxyl terminal region of corticotropin (ACTH), (Ala34-Phe-Pro-Glu-Leu-Phe39), a region of the hormone conserved during evolution, served as an antigen for the production of a sequence-specific antiserum. In a radioimmunoassay, peptides that extend toward the amino terminal from Ala34, such as [Tyr,Gly]-ACTH34-39, ACTH18-39, and ACTH, had greater affinity for the antibody, which suggests that the antiserum recognizes the peptide bond preceding the alanyl residue. The assay readily detects 30 to 50 pmol of ACTH per liter with an incubation of only 3 h, and the antiserum cross reacts with larger molecular mass forms of the hormone. The amount of immunoreactive ACTH extracted by adsorption onto silicic acid from rat and human plasma was only 0.36 to 0.79 of that detected by a mid-region ACTH assay, which suggests proteolytic degradation at the carboxyl terminus of ACTH.

Adrenocorticotropic Hormone↗
PubMed1980

A neuropeptide in mammalian tissues with physalaemin-like immunoreactivity.

Erspamer et al. isolated several structurally related non-mammalian peptides, termed tachykinins, with biological activities similar to substance P (refs 2, 3). This similarity is due to a common COOH-terminal region, whereas the specific action of each member of the group depends on its unique NH2-terminal sequence. Based on these properties, parallel bioassays using numerous smooth muscle preparations and physiological parameters allow them to be generally distinguished. However bioassays are time consuming and not highly specific. Thus, we developed a rapid physalaemin-specific radioimmunoassay that led to the initial discovery of a substance in mammalian tissues with an immunoreactivity resembling that of the original amphibian peptide. We now present data on the distribution, localization and partial characterization of physalaemin-like immunoreactivity (PSLI) in tissues of several mammalian species.

Animals↗