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)

Previously, we reported that pancreatic acini have specific receptors for the insulin-like growth factors (IGF) I and II. We now report that the binding of 125I-labeled IGF II to mouse pancreatic acini is maximally increased by 100 nM insulin (51%) and is maximally reduced by 10 nM cholecystokinin octapeptide (CCK8) (34%), but is not affected by other regulatory peptides such as somatostatin or glucagon. Since many polypeptide hormones are internalized, we determined whether this regulation of IGF II binding occurred via a change in internalization. Acid washing or trypsinization has been shown to remove surface-bound hormone while the acid- or trypsin-resistant radioactivity represents internalized radioligand. Insulin increased and CCK8 decreased the internalization of IGF II as determined by these techniques. Studies of IGF II binding to acini at low temperature (15 degrees C) and binding to particulate fractions from acini were also consistent with the effect of insulin to increase and CCK8 to decrease the internalization of IGF II. When insulin and CCK8 were added together, the inhibitory effect of CCK8 predominated, indicating that CCK8 acted distal to the effect of insulin. Several lines of evidence suggest that this effect of CCK8 was via the CCK receptor and was mediated via a change in intracellular Ca2+: the effect of CCK8 on inhibiting IGF II binding was blocked by the cholecystokinin antagonist N2,O2'-dibutyryl cGMP; the cholinergic agent carbachol (1-100 microM), which acts through the muscarinic receptor to increase intracellular Ca2+, also inhibited IGF II binding; the Ca2+ ionophore A23187 (1-5 microM) mimicked the effects of CCK8 and carbachol. These data indicate, therefore, that CCK8 and possibly insulin may regulate the internalization of IGF II via intracellular Ca2+. Moreover, the data raise the possibility that alterations of hormone internalization may be a general phenomenon of hormone-hormone interaction.
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PMID:Effect of intracellular Ca2+ on insulin-like growth factor II. internalization into pancreatic acini. Roles of insulin and cholecystokinin. 609 32

The effects of 23 agonists on the rates of cellular 32P efflux and lactate dehydrogenase (LDH) release were tested in a perfused rat heart preparation which had been prelabelled in vitro with [32P]Pi. Some 13 compounds produced detectable changes at high doses within 10 min, and in most cases a polyphasic response was observed. Six classes of compound gave rise to substantial effects, as follows. Catecholamines and glucagon produced a transient initial stimulation of Pi efflux, followed by a long-term inhibition of Pi transport and an increased rate of LDH release. These effects were clearly different from the response seen after treatment with dibutyryl cyclic AMP, which had a slower, stimulatory, effect on Pi output in doses which gave rise to a pronounced inotropic effect, and produced a marked increase in both coronary flow and LDH release. Carbachol also gave rise to a large transient stimulation of Pi efflux, which was followed by smaller sustained increase in Pi output without any obvious effect on LDH release. Dibutyryl cyclic GMP had no effect on Pi efflux or LDH release. Insulin decreased the rate of Pi efflux, although the loss rate partially recovered towards the control value after prolonged exposure to the hormone. Insulin had no obvious inotropic effects and produced no change in the rate of LDH release. Corticosteroids increased the rate of Pi efflux, although the loss rate partially declined towards the control value with prolonged exposure to the hormones. Corticosteroids produced a very slight inotropic response, and large doses sometimes increased the rate of LDH release from the tissue. Aldosterone slightly stimulated Pi output. A small, transient and somewhat variable stimulation of Pi efflux was observed with vasopressin and angiotensin, whereas tri-iodothyronine was slightly inhibitory, but adenosine, histamine, spermidine, des-Asp1-angiotensin, prolactin, parathyroid substances, calcitonin and somatostatin had no significant effects under our experimental conditions. Ouabain stimulated Pi efflux in doses that had no detectable inotropic effect. It is suggested that Pi efflux involves the electroneutral transport of NaH2PO4 across the cardiac plasmalemma and that many of the hormonal effects might be explained by changes in the intracellular [Na+] and pH in addition to changes in the intracellular [Pi].
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PMID:Some hormonal effects on myocardial phosphate efflux. 609 15

Somatostatin has been shown to inhibit the release of various polypeptide hormones including insulin, glucagon, gastrin, thyroid stimulating hormone, and growth hormone. The mechanism by which somatostatin inhibits the release of these various polypeptide hormones has not been fully elucidated. It has been reported that somatostatin increases the level of the second messenger cyclic GMP in rat brain and in the anterior pituitary gland. The present investigation was designed to determine if these responses seen in the anterior pituitary gland and brain were due to activation of guanylate cyclase [GTP-pyrophosphate lyase (cyclizing), E.C.4.6.1.2.], the enzyme that catalyzes the formation of cyclic GMP. Somatostatin at a concentration of 2 pM enhanced guanylate cyclase activity two-fold in rat cerebrum and anterior pituitary gland. This enhancement of guanylate cyclase activity was also seen in rat liver, pancreas, stomach, and small intestine at the same concentration of somatostatin. Increasing the concentration of somatostatin to 20 microM, caused a marked inhibition of guanylate cyclase activity in all these tissues. Dose-reponse curves done on gastric guanylate cyclase activity revealed that over a concentration range of 2 pM to 0.2 microM, somatostatin had a stimulatory effect on guanylate cyclase activity while at concentrations above 10 microM somatostatin was inhibitory to guanylate cyclase activity. The biphasic pattern of enhancement of guanylate cyclase activity at lower concentrations of somatostatin and inhibition at higher concentrations may help to explain some of the discrepancies seen with previous investigations with somatostatin, hormone release, and cyclic nucleotide metabolism.
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PMID:The interrelationship of somatostatin and guanylate cyclase activity. 611 Jan 70

Serotonin release from rabbit enterochromaffin cells located in the mucosal epithelium of the small intestine was studied in vitro. Serotonin release from both the serosal and mucosal sides of the small intestine was measured. The addition of muscarinic but not nicotinic cholinergic agonists to the serosal medium resulted in a large but transient increase in serotonin release from the serosal but not the mucosal side of the intestine. Mucosal addition of these agents was ineffective. Serotonin release stimulated by the cholinergic agonist carbachol appeared to be dependent upon influx of extracellular Ca++ for the following reasons: 1) depletion of serosal Ca++ inhibited carbachol-stimulated release; 2) carbachol-stimulated serotonin release was blocked by the inorganic calcium channel blockers Co++, Ni++, Cd++, La and Gd; and 3) serosal serotonin release was increased by the Ca++ ionophore, ionomycin, and by Ba++. The addition of 8-bromoadenosine cyclic AMP or the phosphodiesterase inhibitor, 3-isobutyl-1-methylxanthine, to the serosal medium produced a sustained elevation of serosal serotonin release. 8-bromoadenosine-cyclic AMP-stimulated release was not blocked by depleting extracellular Ca++. Forskolin, a compound which stimulates adenylate cyclase, also stimulated serosal serotonin release. 8-bromoadenosine-cGMP had no effect on serotonin release. Somatostatin (10(-8)-10(-6) M) caused a dose-dependent inhibition of carbachol-stimulated serotonin release. Somatostatin (10(-6) M) only partially inhibited serotonin release stimulated by 8-bromoadenosine-cyclic AMP, 3-isobutyl-1-methylxanthine and forskolin and had no effect on release stimulated by Ba++. The results suggest potential roles for both calcium and cyclic nucleotides in the regulation of serotonin release.
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PMID:Regulation of serotonin release from rabbit intestinal enterochromaffin cells. 614 Mar 9

Somatostatin binding to its receptors on rat pancreatic acinar membranes was characterized with [125I-Tyr1]somatostatin. Binding at 24 degrees C was rapid reaching a maximum after 60 min and was reversible upon the addition of 1 microM unlabeled ligand. Scatchard analysis revealed a single class of binding sites, with a Kd of 0.32 +/- 0.03 nM and a binding capacity of 600 +/- 54 fmol/mg of protein. Specificity for the somatostatin was demonstrated with the inhibition of labeled hormone binding by somatostatin analogs in proportion to their biological activities. When [125I-Tyr1]somatostatin was cross-linked to its receptors with the photoreactive cross-linker n-hydroxysuccinimidyl-4-azidobenzoate, the hormone was associated with Mr = 90,000 protein. Similar mobilities of the radioactive band were observed in the presence and absence of dithiothreitol. In contrast to other unrelated peptides, cholecystokinin (CCK) and its analogs directly reduced [125I-Tyr1] somatostatin binding to isolated membranes. The effect of CCK was one-half-maximal at 3 nM and maximal at 100 nM. In the presence of 3 nM CCK8, the binding capacity for somatostatin was decreased to 237 +/- 39 fmol/mg of protein without a significant change in affinity. Dibutyryl cyclic GMP, a CCK receptor antagonist, blocked this action of CCK8 indicating that the CCK receptor mediated the decrease in [125-Tyr1]somatostatin binding. In contrast cerebral cortex membranes, which also possess a somatostatin receptor, were not regulated by CCK. These results indicate, therefore, that 1) purified pancreatic acinar plasma membranes contain specific receptors for somatostatin, 2) the receptor has an apparent Mr of about 90,000, and 3) the binding of somatostatin to its receptor on pancreatic plasma membranes is regulated by CCK analogs acting via the CCK receptor.
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PMID:The somatostatin receptor on isolated pancreatic acinar cell plasma membranes. Identification of subunit structure and direct regulation by cholecystokinin. 614 17

Patients with chronic recurrent pancreatitis were examined for the blood content of insulin, glucagon, somatostatin (SS), somatotropin (STH), cAMP and cGMP. The blood content of insulin, glucagon and STH was normal, that of SS and cAMP elevated, and that of cGMP lowered. In severe pancreatitis, the endocrine part of the pancreas was activated. The relationship was established between the level of amylasemia and the activity of islet cells and the blood content of cGMP. The compensatory importance of hypersecretion of SS and glucagon for pancreatitis exacerbation is demonstrated. The role of cyclic nucleotides in the pancreatic activity is discussed.
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PMID:[Pancreatic hormones and cyclic nucleotides in the blood in chronic recurrent pancreatitis]. 615 52

The effects of somatostatin on GH secretion, cyclic AMP and cyclic GMp concentrations in dispersed bovine anterior pituitary cells were studied following activation of adenylate cyclase with cholera toxin and inhibition of phosphodiesterase with isobutylmethylxanthine (IBMX). Cholera toxin (10(-5)M) increased intracellular cyclic AMP concentration 10-fold and cyclic GMP concentration 3-fold relative to control, and stimulated the secretion of GH. IBMX (10(-4) M) als increased intracellular concentrations of both cyclic AMP and cyclic GMP and the secretion of GH and potentiated the actions of cholera toxin particularly in raising intracellular cyclic AMP concentrations which were elevated 40-fold in the presence of cholera toxin and IBMX. Somatostatin (5 X 10(-7) M) completely prevented GH secretion elicited by cholera toxin and/or IBMX. Somatostatin was without effect on control cyclic AMP and cyclic GMp concentrations and on the increases in both cyclic AMP and cyclic GMP caused by cholera toxin and by IBMX alone, or in combination. The data suggest that bovine GH secretion is increased when concentrations of either or both cyclic nucleotides are elevated within the cells, although incubation of cells with extracellular concentrations of cyclic AMP and cyclic GMP derivatives up to 2 x 10(-3) M caused only small changes in GH release. We suggest that somatostatin inhibits cholera toxin-induced bovine GH secretion by preventing activation of the secretory process by either cyclic AMP or cyclic GMP.
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PMID:Role of cyclic nucleotides in the inhibition of growth-hormone secretion by somatostatin. 616 35

Somatostatin, substance P, cyclic AMP and cyclic GMP were determined in the cerebrospinal fluid of patients with Huntington's disease, in first generation relatives of choreic patients and in neurological control patients. Substance P levels were not significantly altered, but somatostatin levels were markedly decreased both in affected patients and symptom-free offspring. Cyclic AMP was decreased only in patients with advanced stages of the disease while cyclic GMP was normal. Evidence is discussed which may support a role of somatostatin deficiency in the pathophysiology of chorea.
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PMID:Huntington's chorea-- measurements of somatostatin, substance P and cyclic nucleotides in the cerebrospinal fluid. 616 83

The action of natural and synthetic somatostatin-(1--28), [Nle8]somatostatin-(1--28), somatostatin-(15--28), and somatostatin-(1--14) was examined in dispersed acini from guinea pig pancreas. At high concentrations, the 28-amino acid form of somatostatin increased amylase release, outflux of 45Ca, cellular cGMP, and to a lesser extent cellular cAMP. The increase in amylase release was suppressed by dibutyryl cGMP but was not modified by theophylline or atropine. Binding of 125I-labeled [Thr28, Nle31] cholecystokinin-(25--33) was inhibited by [Nle8]somatostatin-(1--28). These effects required the entire 28-amino acid peptide and appeared to result from occupation of cholecystokinin receptors. It is postulated that they involve interactions between the C-terminal and the N-terminal sequences of the molecule with the participation of the amino acid in position 8. At low concentrations, natural and synthetic forms of somatostatin-(1--28) and somatostatin-(15--28) inhibited secretin- and vasoactive intestinal peptide (VIP)-stimulated increases in cellular cAMP concentration. No difference was found between the potency of somatostatin peptides, indicating that the tetradecapeptide somatostatin-(15--28) is sufficient to exert an inhibitory action on secretin- and VIP-stimulated cellular cAMP concentration. By contrast, the somatostatin fragment S-(1--14) was inactive on pancreatic cellular function.
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PMID:Bimodal regulation of pancreatic exocrine function in vitro by somatostatin-28. 619 25

The immunofluorescent localization of cyclic 3',5'-guanosine monophosphate (cyclic GMP) in rat superior cervical ganglion has been compared to postganglionic neurons having immunoreactivity to neuropeptides. Cyclic GMP-positive somata are equally distributed among cell bodies fluorescent for substance P, somatostatin, and methionine-enkephalin. 40% of the total number of cells stained for each peptide demonstrate co-incident cyclic GMP localization, suggesting a large majority of the neurons employ non-cyclic GMP mechanisms.
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PMID:Co-localization of cyclic GMP in superior cervical ganglion with peptide neurotransmitters. 619 37


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