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Biomedical subjects

W Vale

Publications and source records attributed to W Vale.

At least 433 records · Page 24Linked to original sources
PubMed1979

Isolation and characterization of somatostatin from pigeon pancreas.

Most of the somatostatin-like activity from pigeon pancreas was found to correspond to small species with an apparent molecular weight of 1500--2500. This species was isolated under conditions minimizing intermolecular interactions and protease activities. The isolated product was characterized by two somatostatin radioimmunoassays, a bioassay, endgroup determination, and amino acid analysis. The structure of the isolated compound was determined to be H-Ala-Gly-cyclo-(Cys-Lys-Asn-Phe-Phe-Trp-Lys-Thr-Phe-Thr-Ser-Cys)-OH. Additionally, small amounts of des-Ala1-somatostatin, a possible degradation product of pancreatic somatostatin, and a large somatostatin-like species with an apparent molecular weight of 11,000--12,500 were detected. It is concluded that the main somatostatin-like polypeptide isolated from pigeon pancreas is identical to the mammalian hypothalamic tetradecapeptide somatostatin.

Amino Acid Sequence↗
PubMed1979

Somatostatin analogs inhibit somatostatin release.

To determine if, like insulin, somatostatin inhibits its own secretion from the pancreas, nonimmunoreactive analogs of somatostatin were perfused in an isolated dog pancreaticoduodenal preparation using a nonrecirculating system. [D-Trp8-D-Cys14]somatostatin, at a concentration of 200 ng/ml, blocked the response of somatostatin-like immunoreactivity (SLI) to cholecystokinin and arginine. When perfusion of the analog was discontinued, SLI release increased. At a concentration of 0.1 ng/ml, des Asn5-[D-Trp8]somatostatin lowered SLI levels significantly without significantly reducing glucagon levels. At a concentration of 1 ng/ml, des Asn5-[D-Trp8]somatostatin significantly inhibited SLI as well as insulin and glucagon release. Perfusion of glucagon at a concentration of 10 ng/ml failed to overcome the blockade of SLI and insulin release caused by 50 ng/ml des Asn5-[D-Trp8]somatostatin. The results are compatible with a direct inhibitory effect of somatostatin analogs upon SLI release and raise the possibility of a self-inhibiting action of the native hormone.

Animals↗
PubMed1979

Somatostatin: central nervous system actions on glucoregulation.

Somatostatin (SRIF) has been tested for its actions on the central nervous system to affect glucoregulation. In doses ineffective when given systemically , SRIF and SRIF analogs given intracisternally (ic) reduce hyperglycemia and hyperglucagonemia after ic bombesin administration. The SRIF analog, des-AA1, 2, 4, 5, 12, 13-[D-Trp8]SRIF, decreases plasma insulin and elevates plasma glucose and glucagon when given systemically. However, when given ic, this peptide prevents the rise in glucose and glucagon after ic bombesin administration and is 10 times more potent than SRIF in reducing bombesin-induced hyperglycemia. Other analogs of SRIF and various unrelated peptides were found to be ineffective in reducing bombesin-induced hyperglycemia. des-AA1, 2, 4, 5, 12, 13-[D-Trp]SRIF prevented the hyperglycemia induced by surgical stress or by ic administration of beta-endorphin or carbacol. des-AA1, 2, 4, 5, 12, 13-[D-Trp]SRIF given ic did not prevent hyperglycemia induced by systemic administration of epinephrine, arginine, or glucagon. These studies suggest that SRIF and its analogs may act within the brain to affect glucoregulation.

Animals↗
PubMed1979

Chronic effects of [D-Trp6,Pro9-NEt]luteinizing hormone-releasing factor on reproductive processes in the male rat.

Chronic administration of a potent LRF agonist, [D-Trp6,Pro9-NEt]LFR (A), to intact adult male rats induced a dose-related decrease in testicular and accessory organ weights, diminished production of testosterone (T), and disrupted tubular morphology, indicative of suppression of spermatogenesis. Transient elevations of plasma progesterone levels and a marked reduction of PRL secretion were also observed in A-treated rats. The effects of A on testicular weights, T levels, and seminiferous tubule morphology were already apparent 3 days after the first injection. Administration of A was equally effective when administered daily or at 1- to 4-day intervals in lowering steroid levels and testicular weights. After a 1-week daily exposure to A, seminal vesicles and prostate weights as well as T levels returned to control values within 1--2 weeks. Testicular weights, however, were still depressed 4 weeks after cessation of treatment, and germinal epithelium was disrupted in 30--40% of the tubules. Measurement of T and LH plasma levels after each daily injection of A indicated a blunting of succeeding A-induced elevations of LH and T, which lasted up to 72 h after a single administration of A. The observation that cultured pituitary cells repeatedly exposed to A showed a similar blunting of LRF-induced LH elevation suggests that the decrease in pituitary responsiveness was not exclusively due to steroid feedback. Administration of T propionate to A-treated intact rats was unable to restore normal testicular weights and seminiferous tubule morphology, whereas in hypophysectomized rats, T propionate maintained qualitatively normal spermatogenesis even in the presence of A. These results coupled with the observation that high levels of hCG and PMS gonadotropin had effects similar to those of A on the tubular morphology of intact rats suggest the importance of pituitary secretion in mediating the deleterious effects of A on reproductive functions in the male rat.

Animals↗
PubMed1979

Isolation and characterization of somatostatin from anglerfish pancreatic islet.

Somatostatin was purified from anglerfish pancreatic islets using acetic acid extraction, gel filtration (Bio-Gel P-10), ion exchange chromatography (CM Bio-Gel A), and reversed phase high pressure liquid chromatography. The resulting peptide was characterized by RIA, bioassay, and determination of amino acid composition. Anglerfish islet somatostatin was found to possess an amino acid composition and immunological and biological activities equivalent to synthetic somatostatin. Sequence analyses revealed that the primary structure was H-Ala-Gly-cyclo-[Cys-Lys-Asn-Phe-Phe-Trp-Lys-Thr-Phe-Thr-Ser-Cys]-OH. These results demonstrate that anglerfish islet somatostatin has the same primary structure as somatostatin from all other sources characterized to date.

Amino Acid Sequence↗
PubMed1978

Properties of endogenous somatostatin-like immunoreactivity and synthetic somatostatin in dog plasma.

Somatostatin-like immunoreactivity (SLI) in the peripheral venous plasma of dogs and in their pancreatic and gastric venous effluents was characterized and compared with synthetic somatostatin. Both endogenuous plasma SLI and somatostatin added to plasma were eluted from Sephadex gels at pH 8.8 in the 150,000--200,000-mol wt region but at pH 2.5 both appeared in the 1,500--2,000-mol wt region. The SLI released from the isolated dog pancreas perfused with plasma-free buffer was eluted entirely as a 1,600-dalton polypeptide, but when the pancreas was perfused with plasma, SLI was eluted in the 150,000--200,000-mol wt zone. Affinity chromatography of plasma samples on immobilized antibodies directed against the central portion of the somatostatin molecule (residues 5--9 and 11) removed approximately equal to 90% of both endogenous SLI and somatostatin added to plasma, but neither was removed by affinity chromatography on antibodies directed against the NH2-terminal region of somatostatin (residues 1--4). The SLI from plasma and from pancreas perfusate isolated by affinity chromatography was identical in molecular size, charge, and immunometric properties to synthetic somatostatin. It is concluded that endogenous SLI is secreted by the pancreas and stomach in a form not distinguishable from synthetic somatostatin, but circulates in plasma bound to large molecular weight components; the NH2-terminal residues of somatostatin appear to be important in this binding.

Animals↗
PubMed1978

The effect of bombesin and related peptides on prolactin and growth hormone secretion in the rat.

Bombesin and other related peptides isolated from the skin of anuran species and found in mammalian brain stimulate PRL and GH release in steroid-primed male rats. On a molar basis, bombesin and alytesin are the most active peptides in this assay system. Their PRL- and GH-releasing activity is not affected by the type of anesthetics used, but their minimal effective dose is lower after intravenous administration as compared with intracisternal administration. The in vivo stimulatory effect of bombesin on PRL secretion is not modified by the histamine antagonist diphenhydramine or the opiate antagonist naloxone. By contrast, naloxone reverses the GH-releasing activity of bombesin, suggesting an opiate-dependent mechanism of action of this peptide on GH secretion. The absence of an in vitro effect of bombesin and related peptides on PRL and GH secretion and a minimal effective dose of approximately 30 ng in bombesin and alytesin administered in steroid-primed rats, make them the most active peptides reported so far to act on the brain to modify PRL and GH secretion.

Animals↗
PubMed1978

Somatostatin content of the median eminence in female rats with lesion-induced disruption of the inhibitory control of growth hormone secretion.

These experiments were designed to determine whether brain lesions which elevate nonstress plasma levels of GH and disrupt stress-induced suppression of GH secretion in female rats affect the median eminence content of somatostatin. Some rats received lesions in the medial or lateral preoptic-anterior hypothalamic area (PO-AHA), while others received anterior hypothalamic cuts. Sham-operated and intact rats served as controls. GH and somatostatin were measured by RIA. Medial but not lateral PO-AHA lesions caused elevated nonstress plasma GH levels at 2, 14, 17, and 23 weeks after surgery, but normal levels were obtained at autopsy at 27 weeks. These lesions compromised GH responses to stress at 14 and 23 weeks. Rats with anterior hypothalamic cuts showed elevated nonstress GH levels at 17, 23, and 27 weeks after surgery and loss of the GH response to stress at 14 and 23 weeks. Median eminence content of somatostatin was reduced approximately 80% in rats with medial PO-AHA lesions or anterior cuts. Whereas medial PO-AHA lesions were associated with normal body length and weight and evidence of estrogen secretion, anterior hypothalamic cuts produced increased linear growth and body weight and signs of functional castration. These results suggest that the effects of lesions which cause prolonged elevation of nonstress GH levels and disruption of the GH stress response are due to interference with somatostatin neurons located in the medial PO-AHA. Somatostatin content of the median eminence seems to depend largely on connections originating in or traversing the medial PO-AHA.

Animals↗