Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P61278 (somatostatin)
 22,083 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Rat brain aminopeptidase activity was solubilized from membranes by incubation with thiols. This novel procedure resulted in the release of the same two aminopeptidases (MI and MII) previously shown to be solubilized by the nonionic detergent Triton X-100. The solubilized aminopeptidases MI and MII were resolved by ion-exchange chromatography and further purified by hydroxylapatite chromatography. Aminopeptidase MI was shown to hydrolyze only the beta-naphthylamides of arginine and lysine whereas aminopeptidase MII exhibited a broad specificity with respect to amino acid beta-naphthylamides. Only aminopeptidase MII hydrolyzed Leu-enkephalin at a significant rate, indicating that this enzyme can account for the membrane-bound enkephalin aminopeptidase activity. The enkephalin-degrading aminopeptidase is potently inhibited by opioid (alpha-neo-endorphin and dynorphin) as well as nonopioid (substance P, somatostatin, and angiotensin I) peptides in the range of 0.2-2.0 microM. The regional distribution of aminopeptidases MI and MII in rat brain are rather different, with aminopeptidase MII distribution more closely paralleling the distribution of opiate receptors.
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PMID:Characterization of membrane-bound aminopeptidases from rat brain: identification of the enkephalin-degrading aminopeptidase. 388 43

We have recently shown that synthetic rat atrial natriuretic factor (ANF) directly inhibits mineralocorticoid and glucocorticoid secretion in cultured bovine adrenal cells with a potency of 100 pM. [125I]iodo-ANF was used in the present study to characterize potential receptor sites in bovine zona glomerulosa membranes. ANF binds to a class of high affinity binding sites with a pK of 10.2 and a density of 1.3 pmol/mg protein. Detailed competition curves with ANF document a class of high affinity sites with a pK of 10.2 and also a second class of lower affinity sites with a pK of 8.5. Nonspecific binding amounts to less than 10% of [125I]iodo-ANF binding at concentrations less than 100 pM. High affinity binding of [125I]iodo-ANF is reversible with a half-time of association of 15 minutes at 25 pM and a half-time of dissociation of 140 minutes. Monovalent cations Na, Li and K equipotently enhance [125I]iodo-ANF specific binding. Divalent cations Mg, Ca and Mn also increase [125I]iodo-ANF specific binding, with Mn being the most active cation. No effect of guanine nucleotide could be detected on ANF binding. The binding of [125I]iodo-ANF is very specific and is not inhibited by 1 microM angiotensin II, ACTH, VIP, somatostatin, Leu-enkephalin, dynorphin or by the N-terminal of POMC. The N-terminal fragment ANF-(1-16) is also completely inactive. Reduction of the disulfide bridge of ANF inactivates the peptide. This enabled the development of a highly specific radio-receptor assay for ANF with a minimum detectable dose of 2 femtomoles. The results document the specific receptor involved in the potent inhibitory effect of ANF on adrenal steroidogenesis and indicate that bovine adrenal zonal glomerulosa provide a highly sensitive system for studying the recently discovered atrial natriuretic factor.
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PMID:Characterization of specific receptors for atrial natriuretic factor in bovine adrenal zona glomerulosa. 609 38

An in vitro dispersed hypothalamic cell system was developed and utilized to investigate the effect of exposure to cold stress prior to sacrifice on release of somatostatin-like immunoreactivity (SRIF-LI). Exposure of the rats to cold stress prior to sacrifice significantly increased basal (or control) release of SRIF-LI from dispersed hypothalamic cells. The endogenous opiate peptides (beta-endorphin, Met-enkephalin and Leu-enkephalin)significantly inhibited the basal release of SRIF-LI from dispersed hypothalamic cells obtained from rats exposed to the cold prior to sacrifice. Naloxone, a specific opiate antagonist, had no effect on basal release but blocked inhibition by the endogenous opiate peptides. In marked contrast, the endogenous opiate peptides had no effect on basal release of SRIF-LI from dispersed hypothalamic cells of rats exposed to room temperature prior to sacrifice.
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PMID:Opiate peptides modulate somatostatin release from dispersed hypothalamic cells. 612 May 3

A role for the enkephalins in the regulation of gastric somatostatin (SLI) secretion has been investigated in an isolated perfused rat stomach model. Both methionine- and leucine-enkephalins caused a dose-dependent inhibition of gastric inhibitory polypeptide (GIP) stimulated SLI secretion. Leu-enkephalin was one order of magnitude less potent than met-enkephalin: 50% inhibition by met-enkephalin was at 4 X 10(-9) M and with leu-enkephalin 3.5 X 10(-8) M. Naloxone (100 nM) had no effect on basal secretion but blocked the inhibitory action of met-enkephalin (1 nM or 1 microM). Vagal stimulation (7 V, 10 Hz, 5 ms) inhibited GIP-stimulated SLI release. Administration of naloxone partially reversed this inhibition, suggesting that endogenous opioids were at least partially responsible for vagally induced inhibition. A number of possible pathways by which endogenous enkephalins may modulate SLI release have been proposed.
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PMID:Enkephalinergic control of somatostatin secretion from the perfused rat stomach. 613 72

Specific binding sites for somatostatin have been characterized in cytosolic fraction of rat intestinal mucosa by using 125I-labelled Tyr11-somatostatin and a variety of physicochemical conditions. The binding depended on time, temperature and pH, and was reversible, saturable and specific. At apparent equilibrium, the specific binding of 125I-Tyr11-somatostatin was competitively inhibited by native somatostatin in the 1 nM-4 microM concentration range. Binding studies suggested the presence of two classes of binding sites: a class with high affinity (Kd = 0.07 microM) and low capacity (4.6 pmol/mg protein) and a class with low affinity (Kd = 1.05 microM) and high capacity (277 pmol/mg protein) at 25 degrees C. Somatostatin exhibited competitive inhibition of tracer binding, while neuropeptides such as neurotensin, substance P, Leu-enkephalin, and vasoactive intestinal peptide were ineffective. The presence of somatostatin binding sites in cytosolic fraction of intestinal mucosa, together with the known occurrence of somatostatin in D-cells and nerve endings in the small intestine, strongly suggest that this peptide may be involved in the physiology and physiopathology of intestinal epithelium.
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PMID:Characterization of somatostatin binding sites in cytosolic fraction of rat intestinal mucosa. 614 67

The demonstration of depolarization-induced release of substance P, Met- and Leu-enkephalin, somatostatin, neurotensin, vasoactive intestinal polypeptide and cholecystokinin-like material from various regions of rat brain in vitro supports the hypothesis that these and other neuropeptides may act as neurotransmitters. In each case the stimulus-evoked release, but not the basal release, of peptide was dependent on the presence of calcium ions in the external medium. The stimulus-evoked release of substance P from nerve terminals in rat substantia nigra may be regulated by presynaptic gamma-aminobutyric acid (GABA) receptors. The possible existence of presynaptic opiate receptors on substance P-containing sensory nerve terminals may offer an explanation for the analgesic effects of opiates at spinal cord level, and for the existence of enkephalin neurons in substantia gelatinosa. Capsaicin releases substance P from spinal cord nerve terminals and may impair their function, while having no effect on substance P neurons in supraspinal regions. The possibility of cosecretion of peptide and amine products from the same cells is discussed.
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PMID:Regulation of neuropeptide release. 615 55

The presence of peptides in pure cultures of neurons from 8-day-old chick embryo cerebral hemispheres has been investigated by means of specific radioimmunoassays and chromatographic purification. Somatostatin, Met-enkephalin, Leu-enkephalin, and substance P immunoreactive substances have been detected in 8-day-old cultures grown in serum-free culture medium. The peptides were present in the cellular extracts, as well as in the culture medium extracts. beta-Endorphin, thyroliberin, luteinizing hormone-releasing hormone, and ACTH could not be detected. The largest amount was accounted by somatostatin (48 +/- 2 ng/mg protein). Some 60% of the somatostatin-immunoreactive material was found in the culture medium. Met-enkephalin, Leu-enkephalin, and substance P were present at lower concentrations: 1.61 +/- 0.27, 0.24 +/- 0.02, and 0.14 +/- 0.005 ng/mg protein, respectively. The identities of somatostatin- and enkephalin-immunoreactive materials were confirmed by high pressure liquid chromatography. The findings suggest that cultured neurons that express dopaminergic and GABAergic properties contain peptides similar, if not identical, to somatostatin, Met-enkephalin, Leu-enkephalin, and substance P.
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PMID:Presence of somatostatin, enkephalins, and substance P-like peptides in cultured neurons from embryonic chick cerebral hemispheres. 619 58

Inactivation of substance P and its C-terminal hexapeptide analog [p-Glu6]substance P6-11 was studied in rat parotid and hypothalamic slices. It was found that in the parotid slice system the decay of substance P induced K+ release occurs concurrently with a decrease in the biologically active concentration of the peptide in the medium. The inactivation was further studied using [p-Glu6]substance P6-11 as substrate in the parotid and in the hypothalamic slice systems. In both tissue preparations the hexapeptide is degraded to small peptide fragments by metalloendopeptidase. Separation of the peptide fragments by high performance liquid chromatography and determination of their amino acid composition showed that in the hypothalamic slice system the major cleavage of the hexapeptide analog occurs between Phe8-Gly9 with minor cleavage sites between Phe7-Phe8 and Gly9-Leu10. In the rat parotid slice system the major cleavage occurs between Gly9-Leu10 with a minor cleavage site between Phe7-Phe8. The degradation of the hexapeptide analog in the hypothalamic system was inhibited 77% and 67% by treatment with 1 mM p-chloromercuriphenylsulfonate and p-chloromercuribenzoate, respectively, whereas in the parotid system these reagents inhibited the degradation of the hexapeptide only by 15% and 8%. These results may indicate that different proteases in the parotid and hypothalamus are involved in degradation of substance P. Kinetic studies, including the use of various inhibitors as well as competition by the peptide hormones somatostatin, LHRH, TRH and Leu-enkephalin-NH2, revealed that in both tissues the hexapeptide analog is a preferred substrate for degradation by protease of considerable specificity towards the C-terminal sequence of substance P. It is suggested that this metalloendopeptidase may be important in the termination of the substance P response.
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PMID:Substance P degrading systems of rat parotid and hypothalamus. 620 Jan 41

The colocalization of acetylcholine (ACh) and neuropeptides (e.g., substance P and enkephalins) in the splanchnic nerve terminals suggests that these compounds might interact to modulate adrenal catecholamine release. Use has been made of primary monolayer and suspension cultures of bovine adrenal chromaffin cells to investigate postsynaptic receptor interactions between acetylcholine and a number of neuropeptides endogenous to the adrenal medulla and splanchnic nerve. The cells have both nicotinic and muscarinic acetylcholine receptors, but only the nicotinic receptors stimulate catecholamine release. Substance P, somatostatin, and the enkephalins all produced an inhibition of the ACh-evoked secretion of catecholamines, but their potency ranged over 100-fold. Substance P was the most potent with a mean inhibitory concentration (IC50) of 10(-6) M and Leu-enkephalin the least potent with an IC50 greater than 10(-4) M. These pharmacological effects were monitored conveniently by measuring the release of [3H]norepinephrine preloaded into the cells or alternatively, "on-line" by measuring ATP released into an incubation medium containing luciferin and firefly tail extract (luciferase). Of interest, the endogenous enkephalin heptapeptide (Met-enkephalin Arg6-Phe7) and "big" Met-enkephalin (BAM- 22P ) were some 100-fold more effective than Leu- or Met-enkephalin at inhibiting the nicotinic secretin of catecholamines, suggesting that a unique opiate receptor may be involved. Substance P had two distinct actions on the nicotinic response: (1) substance P inhibited acetylcholine-induced release of catecholamines; and (2) substance P protected against acetylcholine-induced desensitization of catecholamine release. With regard to (1), substance P inhibited the secretion of catecholamines and ATP evoked by acetylcholine or nicotine but not that evoked by K+ or veratridine, nor did substance P by itself affect secretion. Substance P appeared to interact with a regulatory site on the acetylcholine receptor - ionophore complex. Substance P receptors on chromaffin cells have similar structural requirements for activation as do substance P receptors in other substance P responsive tissues. With regard to (2), substance P (greater than 5 X 10(-6) M) completely protected against desensitization of catecholamine release produced by acetylcholine (greater than 10(-4) M) or nicotine (greater than 2.5 X 10(-6) M) with no effect on K+-induced desensitization.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Receptors and receptor modulation in cultured chromaffin cells. 620 33

The central nucleus of the amygdala (ACe) in the rat sends a considerable projection to, and receives projections from, the parabrachial nucleus (PB) and the dorsal vagal complex (DVC; the nucleus of the solitary tract and the dorsal motor nucleus of the vagus nerve). In each part of this 'triangle', immunohistochemical staining for the following peptides has been observed in perikarya and fibers: neurotensin, somatostatin, substance-P, Leu-enkephalin and corticotropin-releasing factor. The aim of the present study was to investigate whether any of these peptides are involved in projections to the brainstem from the ACe, and to characterize the distribution of each cell type in the ACe. The results of double retrograde tracing studies indicate that most of the ACe neurons projecting to the PB and DVC are present in the medial part of ACe (ACem), and that many of them project to both the 1 B and the DVC. The combined use of immunohistochemistry with a retrograde fluorescent tracer, True Blue, indicated that the peptide-containing perikarya are found predominantly in the lateral part of ACe (ACe1), and that only a small proportion of neurotensin, somatostatin and corticotropin-releasing factor-stained neurons contained True Blue after injections into the PB or the DVC. The results suggest that most of the fibers in the descending projection from the ACe to the brainstem do not contain the peptides examined here.
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PMID:The organization of projections from the central nucleus of the amygdala to brainstem sites involved in central autonomic regulation: a combined retrograde transport-immunohistochemical study. 620 16


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