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N Ling

Publications and source records attributed to N Ling.

At least 433 records · Page 24Linked to original sources
PubMed1973

Primary structure of somatostatin, a hypothalamic peptide that inhibits the secretion of pituitary growth hormone.

Somatostatin, a peptide isolated from ovine hypothalamic tissue that inhibits the release of radioimmunoassayable growth hormone in vitro from rat or human pituitary cells or in vivo in rats, has the primary structure [Formula: see text]. The structure was established by submitting the carboxymethylated peptide, the carboxymethylated tryptic digest, and the chymotryptic digest of the peptide to Edman degradation. Degradation products were analyzed by amino-acid analysis, as well as in some cases by determination of N-termini by dansylation or by determination of phenylthiohydantoins by mass spectrometry.

Amino Acid Sequence↗
PubMed1972

Primary structure of the ovine hypothalamic luteinizing hormone-releasing factor (LRF) (LH-hypothalamus-LRF-gas chromatography-mass spectrometry-decapeptide-Edman degradation).

The primary structure of ovine hypothalamic hypophysiotropic luteinizing hormone-releasing factor, LRF, has been established as pGlu-His-Trp-Ser-Tyr-Gly-Leu-Arg-Pro-Gly-NH(2) by hydrolysis of the peptide with chymotrypsin or pyrrolidone-carboxylylpeptidase and by analysis of the products by an Edman-dansylation sequencing technique, as well as by mass spectrometry of the derived phenylthiohydantoins. A decapeptide with the proposed primary structure, prepared by total synthesis, gave the same result on sequencing. The synthetic decapeptide possesses the same biological activities as the native ovine LRF. The amino-acid sequence of ovine LRF is identical to that already published for porcine LRF.

Amino Acid Sequence↗
PubMedDate not supplied

Contribution of the amino terminal tyrosine to the interaction of gamma-endorphin with opiate receptors.

The putative behavioral hexadecapeptide, des-Tyr1-gamma-endorphin, has been compared with gamma-endorphin in an in vitro radioreceptor assay utilizing [3H] beta-endorphin as the labeled ligand and rat brain membranes as a source of opiate receptors. Under the conditions used, beta-endorphin and gamma-endorphin exhibit Kd's of 0.4 nM and 58 nM, respectively. The Kd of des-Tyr1-gamma-endorphin was estimated to be 42 micro M indicating that the amino terminal tyrosine in gamma-endorphin contributes about -4 kcal/mol at 30 degrees C to free energy of binding associated with the peptide-opiate receptor interaction. Circular dichroic spectra were obtained, and the only structural element discernible was a possible beta-turn. Thus, at physiological levels it seems unlikely that the des-Tyr1 fragment of gamma-endorphin will exhibit any significant interaction with the opiate receptor.

Animals↗
PubMedDate not supplied

Enkephalin-containing polypeptides are potent inhibitors of enkephalin degradation.

Enkephalin-containing polypeptides derived from pro-enkephalin A, pro-enkephalin B, or pro-opiomelanocortin were inhibitors of enkephalin degradation by aminoenkephalinases purified from cytosol or membranes. Of the peptides, Argo-Met-enkephalin was the most potent inhibitor for the aminoenkephalinases, with an IC50 of about 0.6 microM, it was more effective than bestatin (IC50 = 0.8-1.0 microM). This inhibition was partly due to substrate competition. Argo-Met-enkephalin was hydrolyzed by aminoenkephalinases to form Arg, Tyr, and Gly-Gly-Phe-Met in a substrate-inhibited manner. The hexapeptide also inhibited the breakdown of Arg- and Tyr-beta-naphthylamide by the membrane aminoenkephalinase. Since Argo-Met-enkephalin did not inhibit leucine aminopeptidase, it was a more selective inhibitor than bestatin of Met-enkephalin breakdown by aminopeptidases. Argo-Met-enkephalin inhibited enkephalin breakdown by synaptosomal plasma membranes but not by brain slices. Our data suggest that in addition to their possible role as opioids, the enkephalin-containing polypeptides may be regulators of enkephalin levels.

Aminopeptidases↗
PubMedDate not supplied

des-(1-13) human beta-endorphin interacts with calmodulin.

It is known that the 31-residue neuropeptide beta-endorphin inhibits the calcium-dependent, calmodulin-mediated stimulation of cyclic nucleotide phosphodiesterase activity. The results of this study demonstrate that a non-opiate, synthetic amino terminal deletion peptide, des-(1-13), of human beta-endorphin is also capable of inhibiting the stimulated enzymic activity, but not the basal activity. This inhibition occurs with the same efficacy as the intact 31-residue peptide. Thus, the amino terminal region of beta-endorphin, which is responsible for opiate activity, does not appear to contribute to the calmodulin interaction. Circular dichroic spectroscopy of des-(1-13) beta-endorphin, calmodulin, and mixtures of the two shows that the ellipticity at 221 nm was more negative in the peptide-protein mixture than could be accounted for on the basis of simple additivity of the peptide and calmodulin. This spectral change implies enhanced alpha-helicity concomitant with the peptide-protein association. Helix formation may occur in the peptide since this sequence has the potential to form an amphipathic helix.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMedDate not supplied

The distribution of alpha-melanocyte stimulating hormone (alpha-MSH) in the central nervous system of the rat: an immunohistochemical study. II. Lower brain stem.

The distribution of immunoreactive alpha-melanocyte stimulating hormone (alpha-MSHI) in the rat lower brain stem was examined by indirect immunofluorescence or peroxidase- anti-peroxidase immunohistochemical method using an antiserum against synthetic alpha-MSH. The results confirmed the presence of alpha-MSHI fibers in the midbrain central gray matter and parabrachial area, and demonstrated a much more extensive distribution of these fibers in various parts of the lower brain stem areas previously thought not contain alpha-MSHI fibers. In addition, the commissural nucleus was identified as a new alpha-MSHI neurons-containing site. No alpha-MSHI neurons were seen in other regions of the rat lower brain stem.

Animals↗
PubMedDate not supplied

Attenuation of corticotropin releasing factor-induced hypotension in anesthetized rats with the CRF antagonist, alpha-helical CRF9-41; comparison with effect on ACTH release.

The effect of pretreatment with the corticotropin releasing factor (CRF-41) antagonist, alpha-helical CRF(9-41), on the hypotensive response obtained on peripheral administration of CRF-41 has been assessed in anesthetized Wistar rats. A single IV bolus dose of rat CRF-41 (2 nmol, at 0 min) produced a hypotensive effect which was rapid in onset (-52 mmHg at +1 min) and sustained throughout the 60-min study period (-42, -40, -26 and -16 mmHg at +3, +10, +30 and +60 min, respectively). The antagonist [alpha CRF(9-41)] was administered in consecutive bolus doses of 12.5, 25 and 50 nmol at -15, -10 and -5 min, respectively. This had no effect on mean arterial blood pressure (MABP) or heart rate, nor did it change significantly the magnitude of the initial rapid fall in MABP when CRF-41 was administered (-45 mmHg at +1 min). However, following pretreatment with alpha CRF(9-41), MABP returned to control values within 3 min and the sustained period of hypotension was completely blocked. Administration of CRF-41 resulted in 44% and 142% increases in norepinephrine and epinephrine measured at +60 min. Pretreatment with the antagonist attenuated the rise in circulating catecholamine levels observed after CRF-41 administration. In comparison, pretreatment with the antagonist did not alter the ACTH response to CRF-41 at +1 and +3 min and only reduced ACTH levels by 28% (p less than 0.05), 43% (p less than 0.001) and 41% (p less than 0.01) at 10, 30 and 60 min, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenocorticotropic Hormone↗
PubMedDate not supplied

Immunohistochemical detection of growth hormone-releasing factor in brain.

The concept of a hypothalamic neurohumoral control for anterior pituitary secretion postulates the existence of a growth hormone-releasing factor (GRF) of neuronal origin that stimulates the pituitary gland to release growth hormone (GH). Such a compound has not yet been isolated and characterized from the brain, although there is extensive physiological and biochemical evidence for its existence (reviewed in ref. 2). However, a 44-amino-acid amidated peptide having the physiological properties of GRF as well as chemical similarities was recently isolated from a human pancreatic tumour that had caused acromegaly. Two shorter biologically active fragments of 40 and 37 residues were also isolated. The synthetic replicates of these human pancreas GRF (hpGRF) peptides specifically stimulate GH release in vitro and in vivo. Assuming similarity or identity between the putative hypothalamic GRF and the tumour-derived hpGRF, we have used immunohistochemistry to search for hpGRF-like immunoreactivity in the brain. We report here that antisera against the hpGRF1-40 peptide specifically stain neuronal cell bodies in the arcuate nucleus of the primate hypothalamus, with fibres projecting to the median eminence and ending in contact with portal vessels. This topography is characteristic of a neuronal system elaborating a releasing factor. These results provide evidence that hypothalamic GRF is very similar, if not identical, to hpGRF.

Aged↗
PubMedDate not supplied

Specific depletion of immunoreactive growth hormone-releasing factor by monosodium glutamate in rat median eminence.

A potent and specific growth hormone-releasing factor (GRF) was recently isolated and characterized from a human islet cell tumour of the pancreas that caused acromegaly. Antibodies raised against the synthetic replicate of this peptide have allowed the immunohistochemical identification of GRF-producing neurones within the primate central nervous system. Such neurones are found mainly in the arcuate nucleus in human and monkey hypothalamus, suggesting that this nucleus is a primary source of GRF. We have further investigated this hypothesis by studying the anatomical organization of GRF neurones in rat hypothalamus, using an antibody raised against the recently characterized rat hypothalamic GRF in normal animals and in animals neonatally treated with monosodium glutamate (MSG), a treatment which results in the selective destruction of arcuate nucleus neurones. We present here the results which show that GRF-producing neurones are located mainly in the arcuate nucleus of rats. MSG treatment results in the complete loss of GRF-immunoreactive cell bodies within this nucleus and provokes a selective disappearance of GRF-immunoreactive fibres in the median eminence. These results show that the arcuate nucleus is the origin of the GRF-containing fibres that project to the median eminence and establish the MSG-treated rat as an in vivo model for studying growth hormone secretion in the absence of neurohumoral GRF.

Animals↗