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Biomedical subjects

W Vale

Publications and source records attributed to W Vale.

At least 487 records · Page 27Linked to original sources
PubMed1975

Somatostatin analogs. Relative importance of the disulfide bridge and of the Ala-Gly side chain for biological activity.

Four analogs of ovine somatostatin (SRIF, PSOMATOTROPIN RELEASE INhibiting factor), the sequence of which is H-Ala-Gly-Cys-Lys-Asn-Phe-Phe-trp-Lys-Thr-Phe-Thr-Ser-Cys-OH, have been synthesized by the solid-phase methodology. The compounds were assayed and were found to possess the following somatotropin release inhibiting potencies relative to pure synthetic somatostatin in vitro and in vivo, respectively: [Ala3,14]somatostatin, 0.6 and 2.0%; [SMe-Cys3,14]somatostatin, 4 and 0.6%; [NAc-Cys3]somatostatin, 39 and 105%; [des-Ala1-Gly2]somatostatin, 65 and 71%. The dihydrosomatostatin analogs [NAc-Cys3-H2]somatostatin and [des-Ala1Gly2-H2]somatostatin after two purifications by gel filtration were assessed to be at least 80% homogeneous and had respectively 99 and 89% of somatostatin potencied in vivo. Structure-activity relationships are discussed.

Alanine↗
PubMed1975

Central nervous system effects of hypothalamic peptides.

Intravenous (i.v.) administration of TRF (1 mg/kg) increases the LD50 of pentobarbital (PB) by 25% while the same dose of somatostatin results in a 30% reduction in PB LD50. A similar increase of PB LD50 by TRF was observed in hypophysectomized rats. Mortality was completely abolished in rats receiving TRF (1 mg/kg) ten minutes after a lethal dose of PB (120 mg/kg). Somatostatin (1 mg/kg) decreases strychnine-induced seizure duration and increases strychnine LD50 by 21% while TRF lowers the strychnine LD50 by 28%. These observations are consistent with central nervous system sites of action for TRF and somatostatin.

Animals↗
PubMed1975

Growth hormone release in the rat: effects of somatostatin and thyrotropin-releasing factor.

Morphine sulfate (MS) and pentobarbital (PB) stimulate growth hormone (GH) release in the rat in vivo, but not from enzymatically dissociated anterior pituitary cells in vitro. Somatostatin and thyrotropin-releasing factor (TRF) inhibit the in vivo release of GH induced by MS, with 50% inhibition at ca. 2.3 and 4.6 mug/100 g BW, respectively. Somatostatin and TRF similarly inhibit PB-induced GH release. Prostaglandin E2 stimulates GH release both in vivo and in vitro. Both of these responses are inhibited by somatostatin (50% inhibition at ca. 10 mug/100g BW), but neither is altered by TRF (100 mug/100g BW). Both normal and hypophysectomized rats receiving MS exhibited a rapid vibration of the tail immediately after administration of TRF (30 mug/100g BW). Structural analogs of TRF with low TSH-releasing activity did not inhibit GH release nor induced tail vibration in MS-treated rats. Pyroglutamyl-3-methyl-histidyl-prolinamide, with 8 times the hypophysiotropic potency of TRF, is similarly more potent than TRF in inhibiting GH release and inducing tail vibration in MS-treated rats. These results suggest the following: 1) MS and PB act at a central nervous system (CNS) site to release GH; 2) TRF may act at a CNS site to inhibit MS- and PB-induced GH release; 3) somatostatin has direct pituitary effects on inhibition of GH, but a CNS site of action cannot be excluded; and 4) TRF stimulates tail motor activity in MS-treated rats.

Animals↗