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N Ling

Publications and source records attributed to N Ling.

At least 343 records · Page 19Linked to original sources
PubMed1982

Immunoreactive gamma-melanotropin in rat pituitary and plasma: a partial characterization.

A RIA for the gamma MSH region of proopiomelanocortin has been established and validated. The antiserum was raised to synthetic bovine gamma MSH, and it cross-reacts well with larger polypeptides, including gamma MSH and 16K fragment, which contain the gamma MSH sequence. Gel filtration chromatography of extracts prepared from the anterior and neurointermediate lobes of rat pituitary and from rat plasma reveal two heterogeneous immunoreactive (IR-) forms of gamma MSH in each venue which elute in molecular weight peaks of approximately 11,000 (11K) and 6,000 (6K). Addition experiments indicate that the smaller material is not an artifact generated from the larger form during preparation. By the criterion of retention on affinity columns of Concanavalin A-agarose, these peptides are glycosylated. The 6K form represents 8-17% of the total IR-gamma MSH in the anterior lobe and about 30% of that in the neurointermediate lobe. IR-gamma MSH are released by dispersed rat pituitary cells in response to several of the same secretagogues which modulate the secretion of other proopiomelanocortin-derived peptides. Changes in the plasma and anterior lobe content of IR-gamma MSHs and ACTH resulting from perturbation of the pituitary-adrenal axis are concordant. In particular, the plasma concentration of 6K IR-gamma MSH increases dramatically after imposed stress.

Amino Acid Sequence↗
PubMed1982

Somatostatin-28 is longer acting and more selective than somatostatin-14 on pituitary and pancreatic hormone release.

In the present studies, the large form of somatostatin (SS), SS-28, and an analog [D-Trp22]SS-28 were reproduced by solid phase synthesis, and the time course of their in vivo biological actions was examined in comparison to that of the tetradecapeptide SS-14. Longitudinal profiles of plasma GH immunoreactive insulin (IRI), glucagon, and glucose were obtained from freely moving, chronically cannulated rats after the sc administration of 100 microgram of SS-28, [D-Trp22]SS-28, SS-14, or normal saline. Normal saline-treated animals exhibited the typical pulsatile pattern of GH secretion. The administration of SS-14 resulted in a significant suppression of spontaneous GH surges for only 30 min. In contrast, the administration of SS-28 caused a marked inhibition of spontaneous GH release which persisted for a significantly longer period of time (90 min). At the level of the pancreas, SS-14 inhibited basal IRI release for 45 min. Both SS-28 and [D-Trp22]SS-28 exhibited potent inhibitory actions on basal IRI release for longer periods of time than did SS-14. Plasma IRI levels remained markedly depressed for 60 min after SS-28 administration, and [D-Trp22]SS-28 significantly prolonged the duration of inhibitory activity of the parent compound to 105 min. In contrast to the effects observed on IRI, the time courses of significant inhibition of plasma glucagon were similar in response to SS-14 and SS-28, although [D-Trp22]SS-28 prolonged the duration of the inhibitory action of SS-28. Furthermore, marked hyperglycemia was subsequently observed after the administration of SS-28 and [D-Trp22]SS-28, but not after SS-14 treatment. These results demonstrate that 1) SS-28 is longer acting than SS-14 in inhibiting spontaneous GH and IRI release, 2) D-Trp substitution in position 22 of SS-28 significantly prolongs the duration of inhibition of IRI and glucagon release, and 3) SS-28 compared to SS-14 exhibits selectivity in the time course of action on pancreatic hormone release.

Animals↗
PubMed1982

The in vivo metabolism of somatostatin 28: possible relationship between diminished metabolism and enhanced biological action.

We have compared the metabolism of infused somatostatin 14 (SS14) and somatostatin 28 (SS 28) in anesthetized dogs. After iv infusion of either peptide, plasma SS-like immunoreactivity (SLI) coeluted from Bio-Gel P10 columns with the corresponding synthetic peptide marker. The hepatic extraction, renal extraction, MCR, and plasma half-life of plasma SLI and after SS28 infusion were 11.0 +/- 1.5%, 50 +/- 4.8%, 9.9 +/- 1.4 ml/kg.min, and 2.8 +/- 0.3 min, respectively. Corresponding values after SS14 infusion were 43.1 +/- 7.4%, 82.2 +/- 6.6%, 21.9 +/- 6.5 ml/kg.min, and 1.7 +/- 0.2 min. These differences between SS28 and SS14 were all statistically significant (P less than 0.05). When equimolar amounts of each peptide were given as bolus injections, both led to a significant reduction in portal venous blood flow. After the injection of SS14, the reduction in flow was short-lived and returned to baseline by 4 min. However, between 2-7.5 min after the injection of SS28, the reduction in blood flow was significantly greater than that induced by SS14, and returned to baseline only by 15 min. These studies indicate that the metabolism of plasma SLI is significantly slower during the steady state infusion of SS28 in pharmacological doses than after similar infusions of SS14. SS28 led to a more prolonged reduction in portal blood flow than SS14; this effect is probably due to its slowed metabolism. This suggests that further modification of the SS28 molecule may increase its therapeutic potential by slowing its in vivo metabolism.

Animals↗
PubMed1982

Somatostatin-28(1-12)-like immunoreactivity in the rat.

The distribution of the newly characterized peptide somatostatin-28(1-12) was determined in rat tissues using a radioimmunoassay in which the immune plasma is directed against the C-terminus of the dodecapeptide. In the central nervous system, somatostatin-28(1-12)-like immunoreactivity is highly concentrated in the hypothalamus and the amygdala. In the digestive system, the highest levels of immunoreactivity are found in the stomach, the pancreas and the colon. The immunoreactive material measured in different tissues is the heterogenous: in addition to the dodecapeptide, two N-terminally extended somatostatin-28(1-12) peptides of 4,400 and 8,000 mol wt are also detected by the immune plasma. However, the dodecapeptide itself usually accounts for the majority (66 to 75%) of the total somatostatin-28(1-12)-like immunoreactivity present in those tissues.

Animals↗
PubMed1982

Studies on the structural prerequisites for the activation of the beta-endorphin receptor on the rat vas deferens.

The inhibitory activity of a variety of opioid peptides was tested on the electrically stimulated rat vas deferens. Human beta-endorphin (beta h-EP) was the most potent of the opoioid-like peptides; it produced half-maximal inhibition of the neuromuscular twitching at a concentration of about 100 nM. The potency of beta h-EP was greater than that of camel, porcine, ovine or leucine5 beta h-EP, alpha-N-acetyl beta-ovine-EP was inactive. In contrast to beta-endorphin (beta-EP), methionine and leucine-enkephalin, dynorphin-(1-13), morphine and other narcotic analgesics were devoid of opioid-like activity. Fragments of beta-EP with amino acid deletions at the carboxy end of the molecule were considerably less potent than the parent compound. The fragment beta h-EP 1-21 was 70 times less potent than beta h-EP, whereas the segments beta h-EP 1-19 and beta h-EP 1-16 were both completely inactive. Deletions at the amino terminal of beta-EP yielded inactive compounds. The potency of beta h-EP was reduced in a dose-related fashion by applications of nanomolar concentrations of naloxone or N-allylnormetazocine and by micromolar concentrations of levorphanol or morphine. In decided contrast, opioid peptides such as methionine enkephalin, dynorphin-(1-13), beta-casomorphan derivatives or short chain beta h-EP segments such as beta-EP 1-16, beta-EP 1-19, beta-EP 6-31, beta-EP (1-5)-(16-31), methionine enkephalin plus beta-EP 6-31 or the N-acetyl beta-bovine-EP did not antagonize the inhibitory action of beta h-EP. The present results demonstrate that the rat vas deferens contains opioid receptors with considerable selectivity for beta-EP. It is concluded from this structure activity relationship study that the activation of the beta-EP receptor involves at least two sites of recognition on the beta-EP structure.

Animals↗
PubMed1981

In vivo release of enkephalin from the globus pallidus.

Push-pull cannulae were acutely positioned through previously implanted guides in the globus pallidus of unanesthetized freely moving cats and rats. During slow-flow perfusions, enkephalin release was detected in resting conditions and increased more than 3-fold when both 50 mM K+ and 1.8 mM Ca2+ were present in the perfusing medium. Local perfusion with veratrine also enhanced enkephalin release. Furthermore, in vivo, electrical stimulation of the rat caudo-putamen enhanced enkephalin release in the pallidum. This latter finding is consistent with a functional strio-pallidal enkephalin-containing pathway previously postulated by immunohistochemical or lesion experiments.

Animals↗
PubMed1981

Somatostatin-28, somatostatin-14 and somatostatin analogs: effects on thermoregulation.

Somatostatins, somatostatin-14, somatostatin-28, and desAA [D-Trp8]-somatostatin, with differential potencies, act in the brain to reverse chemical-induced hypothermia and to produce hyperthermia. Somatostatins are more potent and loger acting than prostaglandin E2 in producing hyperthermia. Hyperthermia, induced by somatostatins, is not prevented by previous treatment with the prostaglandin synthesis inhibitor indomethacin. Somtostatins given to obese ob/ob mice prevent development of lethal hypothermia and result in maintenance of euthermia. Continuous infusion of somatostatins results in desensitization to the hyperthermic effects of these peptides. Endogenous somatostatins may be involved in regulation of body temperature.

Animals↗
PubMed1981

Selective effects of somatostatin-14, -25 and -28 on in vitro insulin and glucagon secretion.

The widely occurring tetradecapeptide somatostatin (SRIF-14) has been variously implicated as a neurotransmitter, a neurohormone, a cybernin (local regulatory factor) and a hormone. In the first isolation of SRIF-14 from hypothalamic extracts and subsequent extracts of other tissues, peptides of higher molecular weight but with similar activity have been noted. Recently two such peptides have been characterized as the 28-amino acid SRIF-28 (from porcine gastro-intestinal tract and porcine and ovine hypothalamus and the 25-amino acid SRIF-25 (from ovine hypothalamus), each of which consists of an N-terminal extension of SRIF-14. We now report that SRIF-28 and SRIF-25 are more potent than SRIF-14 in the inhibition of insulin release, but that SRIF-14 preferentially inhibits glucagon release. This suggests that SRIF-28 and SRIF-25 are not mere biosynthetic precursors of SRIF-14 and that their differential release may be physiologically important.

Animals↗
PubMed1981

Isolation and chemical characterization of somatostatin-28 from rat hypothalamus.

A peptide with somatostatin-like immuno- and bioactivity has been isolated from an aqueous extract of 96 800 rat hypothalamic by means of immunoaffinity chromatography, gel filtration and reverse-phase high-performance liquid chromatography (HPLC). Chemical characterization by amino acid analysis, tryptic peptide mapping and retention behavior in two HPLC system showed that the peptide was indistinguishable from somatostatin-28 previously characterized from several species. This evidence suggests that rat hypothalamic somatostatin-28 is identical in structure to porcine and ovine somatostatin-28.

Amino Acids↗
PubMed1981

High biological activity of the synthetic replicates of somatostatin-28 and somatostatin-25.

We have isolated form extracts of ovine hypothalami two molecules characterized as somatostatin-28 and somatostatin-4-28 (referred to as somatostatin-25). They were reproduced by solid hase synthesis. In equimolar ratio and depending upon the experimental conditions, synthetic somatostatin-28 ans somatostatin-25 are 3-14 times more potent than somatostatin-14 to inhibit the basal in vitro secretion of growth hormone or as stimulated by prostaglandin (PGE2). In early studies in vivo, somatostatin-28 and somatostatin-25 are also more potent than somatostatin-14 in inhibiting the secretion of growth hormone acutely stimulated in the rat by injection of morphine; somatostatin-28 is also longer-acting than somatostatin-14. These results suggest that somatostatin-14, as originally isolated, is a biologically active fragment of a larger molecule of greater specific activity; it should be considered as another form of somatostatin with high biological activity present in some tissues and likely secreted y the tissues along with somatostatin-14 and possibly other somatostatin-peptides of diverse sizes.

Animals↗
PubMed1981

The regional distribution of gamma 3-melanotropin-like peptides in bovine brain is correlated with adrenocorticotropin immunoreactivity but not with beta-endorphin.

Immunoreactive (IR)-gamma 3-melanotropin (MSH), -adrenocorticotropin (ACTH) and -beta-endorphin in various areas of bovine brain were measured with their respective radioimmunoassays (RIA). The concentrations of IR-gamma 3-MSH were almost the same as those of IR-ACTH in most areas. Furthermore, in all brain regions, the concentrations of both peptides were lower than those of IR-beta-endorphin. The highest concentration of IR-gamma 3-MSH was found in hypothalamus, followed by thalamus, midbrain and striatum. Gel permeation chromatographic studies showed that the main gamma 3-MSH-like peptide in the hypothalamus, striatum and midbrain was a small form, whose molecular weight is about 4500. These brain gamma 3-MSH-like peptides were also found to be glycosylated.

Adrenocorticotropic Hormone↗
PubMed1981

Development and validation of a radioimmunoassay for beta-endorphin-related peptides.

A radioimmunoassay method suitable for measuring levels of B-endorphin, B-lipotropin and proopiocortin in tissue and plasma extracts was developed and the method was evaluated by using 3 independently prepared antisera. Of the several variables tested the choice of assay buffer and test tubes and the purification of tracer were found to be the most critical in the successful performance of B-endorphin radioimmunoassay. The prevention of degradation of tracer during incubation was also necessary when crude tissue extracts or plasma were assay. The sensitivities of the assays obtained with the 3 antisera utilized (Bendo 2, K2 and RB 100) were 1, 2.8 and 4 fmol B-endorphin per tube. All the antisera crossreacted equimolarly with B-lipotropin. The method was employed to measure the levels of B-endorphin immunoreactivity in rat pituitary and plasma by separating the different immunoreactants by gel filtration. It was found that both pituitary and plasma contain significant amounts of proopiocortin, B-lipotropin and B-endorphin, the molar proportions being 10:33:57 in pituitary and 15:15:17 in plasma, respectively. Both anterior and posterior lobes of rat pituitary were found to contain all the three immunoreactants. However, anterior lobe contained mostly the larger molecules, while posterior lobe was rich in B-endorphin. No absolute levels of the immunoreactants could be obtained due to the heterologous system used. Moreover the elution pattern of the immunoreactivity was found to be dependent on the conditions used for elution in gel filtration: higher proportion of the immunoreactivity eluted like B-endorphin when the elution was done in dissociating conditions (6 M urea) compared to elution with ordinary buffers.

Animals↗
PubMed1981

Gonadocrinins: peptides in ovarian follicular fluid stimulating the secretion of pituitary gonadotropins.

A newly discovered small peptide purified from rat follicular fluid stimulates the pituitary to release FSH and LH in vitro as well as in vivo. Dialysates of crude acid extracts of ovarian follicular tissue and fluid from rats pretreated with PMS gonadotropin stimulate the secretion of both LH and FSH, but not PRL, GH, or TSH, in a pituitary monolayer culture system. This stimulating factor, named gonadocrinin for operational facility, is smaller than 3500 daltons; its biological activity disappears after treatment with trypsin. Gonadocrinin is not recognized by two-antisera binding the decapeptide LRF even though D-Phe2,D-Trp6-LR, an LRF analog antagonist, competitively inhibits the activity of ovarian gonadocrinin. Cultured rat granulosa cells also secret substances with gonadocrinin activity in vitro, indicating that the granulosa cells probably are in vivo the source of gonadocrinin. A crude preparation of gonadocrinin given iv to rats on the second day of diestrus induced secretion of LH comparable to that produced by a 250-ng LRF injection. Gonadocrinin has chemical characteristics different from those of LRF. When purified gonadocrinin or LRF was applied to an identical isocratic high pressure liquid chromatography system, LRF was eluted at a position different from that of gonadocrinin, indicating that, chemically, gonadocrinin is not identical to the hypothalamic decapeptide, LRF.

1-Methyl-3-isobutylxanthine↗
PubMed1981

Isolation and characterization of rat hypothalamic somatostatin-14.

A peptide with somatostatin-like immuno- and bioactivity has been isolated from 1165 rat hypothalami by using antisomatostatin affinity chromatography, gel filtration and reverse-phase high-performance liquid chromatography. The isolated peptide is indistinguishable from synthetic somatostatin-14 with respect to chromatographic properties and amino acid composition. We therefore propose that rat hypothalamic somatostatin-14 is identical in structure to somatostatin-14 found in other species.

Amino Acids↗