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)

1. Dibutyryl cyclic AMP (Db cAMP, 75-500 microgram/kg), injected into the lateral ventricle of the brain of the cat increased blood pressure, heart rate and splanchnic discharge rate. 2. ATP, but not AMP, induced similar changes; GMP in small doses increased blood pressure. 3. A number of drugs are known to activate adenylate cyclase-induced hypertension, tachycardia and increase splanchnic discharge rate. This was shown for TRH, tetracosactide and a new beta2-adrenoceptor stimulant, NAB 365. 4. Injection into the lateral ventricle of theophylline or Ro 7/2956, both inhibitors of phosphodiesterase, similarly increased blood pressure. 5. Histamine administered by the same route induced similar reactions; it is not known if this action was exerted by activation of H1- or H2-receptors. 6. Somatostatin, known to reduce cAMP levels, induced a small but significant decrease in blood pressure. Melanocyte stimulating hormone release inhibiting factor (MIF) and TSH were ineffective. 7. These results provide evidence for the possibility of a role for cAMP in the central regulation of blood pressure at suprabulbar levels.
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PMID:Cyclic 3'5'-adenosine monophosphate and central circulatory control in cats and dogs. 2 Feb 56

The effect of somatostatin on insulin release by incubated slices of rat pancreas was studied. Somatostatin inhibited insulin release induced by arginine/glucose (A/G), glucagon, glibenclamide, pentoxifyllin, 3',5'-adenosine monophosphate (cAMP), phentolamine, and KCl. When A/G was used as a stimulus, the quantial inhibitory effect of somatostatin was not neutralized by progressively increasing glucose concentrations. The alpha adrenergic blocking agent phentolamine, the phosphodiesterase inhibitors theophylline (10 mM) or pentoxifyllin (10 mM), and KCl partially reversed the inhibitory effect of somatostatin on A/G stimulation. The maximal reversal of somatostatin inhibition was obtained when the slices of pancreas were stimulated with A/G in the presence of the calcium ioniphore A23187 plus ATP. These results suggest that the inhibitory effect of somatostatin on insulin secretion could result from calcium translocation in pancreatic beta cells.
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PMID:Studies on the mode of action of somatostatin on insulin secretion. 19 19

Utilizing histones as a substrate and measuring the production of labelled phosphoserine from [gamma 32P-ATP], cAMP stimulated protein kinase activity was found in islet and anterior pituitary secretory vesicles. Cyclic AMP (5 X 10(-7)m)stimulated islet secretory vesicle protein kinase activity as evidenced by a net increase of 32P incorporation into phosphoserine 7.35 +/- 1.68 pmoles/micrograms, (P LESS THAN 9001). Somatostatin (0.1 ng/microgram) decreased 32P phosphoserine production from 10.64 +/- 1.72 to 5.61 +/- 1.26 pmoles/microgram (Pless than .01) by suppressing cAMP stimulated protein kinase activity. In pituitary secretory vesicles, cAMP (5 X 10(-6M) increased 32P incorporation into TCA precipitable protein from 127.3 +/- 8.6 to 202.6 +/- 12.5 pmoles/microgram, P less than .001. With somatostatin (0.2 ng/microgram) there was 55.25+/- 1.95% inhibition of cAMP stimulated protein kinase activity, (P LESS THAN .001). Somatostatin did not inhibit cAMP stimulated protein kinase activity in erythrocyte membrane ghosts nor did somatostatin inhibit the partially purified cAMP dependent protein kinase from cardiac muscle. These data suggest that either (1) a specific somatostatin sensitive dependent protein kinase is present in islet and anterior pituitary secretory vesicles or (2) that a somatostatin receptor is present in these tissues which allows somatostatin to act selectively at these sites. Somatostatin may act by inhibiting the cAMP dependent protein kinase enzme in certain key tissues or subcellular organelles.
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PMID:Somatostatin: selective inhibition of cyclic AMP stimulated protein kinase. 22 50

1. Investigation of the ionic requirements of the in vitro insulin release system, which consists of cod islet plasma membrane and rabbit islet granules incubated at pH 6.5, showed that the presence of Ca(2+) was obligatory for the system to operate.2. Glucose-initiated insulin release was as effective in the presence of beta-gamma-methylene ATP, as it was in the presence of ATP. This analogue of ATP is a substrate neither for adenylate cyclase nor for any known animal membrane proteases. The effect of ATP on glucose mediated release is allosteric.3. Glucose (16 mM)-initiated insulin release was slower than that induced by glucose-6-phosphate (4 mM); 150 and 120 sec, respectively.4. The lag found with glucose-mediated insulin release was dependent upon glucose concentration. The lower the glucose concentration, the longer the lag. With 1 mM glucose the lag extended to 30 min.5. Once insulin release was initiated, the rate and amount of insulin release was independent of the glucose concentration.6. Pre-incubation of membranes with Ca(2+), glucose and ATP prior to the addition of granules, abolished the extended lag that had been obtained with 1 mM glucose. Events in the plasma membrane are the major contributor to the generation of the extended lag.7. The glucose analogue 5'thio-D-glucose, although not able to release insulin, was shown to compete with glucose for the glucoreceptor. By increasing the ratio of analogue to glucose the lag time increased. Thus, the lag time is dependent upon the ;effective' external glucose concentration.8. The max. amount of insulin released by 4 ng of membrane in the presence of glucose (16 mM) was 300 ng. The fact that membranes became refractory to glucose after this max. amount of insulin was released showed that recycling of release sites was not taking place in vitro and that granule: granule interactions were not occurring.9. The 120 sec lag before glucose-6-phosphate-initiated release was independent of glucose-6-phosphate concentration. The rate of insulin release with glucose-6-phosphate was concentration dependent.10. Glucose-6-phosphate did not cause further insulin release from a membrane that had released the max. amount of insulin it was capable of in the presence of glucose. The addition of tolbutamide (10 mM) to such a membrane did cause insulin release. This suggests that glucose and glucose-6-phosphate share a final common pathway.11. Adrenaline and somatostatin did not inhibit glucose-mediated insulin release.
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PMID:An in vitro system for studying insulin release: effects of glucose and glucose-6-phosphate. 33 48

Substance P, somatostatin, enkephalin and vasoactive intestinal polypeptide (VIP) did not mimic the inhibitory responses to non-adrenergic, non-cholinergic nerve stimulation. Substance P (0.1-10 microgram/ml) always caused contraction, enkephalin (0.1-10 microgram/ml) and somatostatin (0.1 microgram/ml) were inactive, while VIP (0.1-1 microgram/ml) produced very slow relaxation, taking about 4 min to reach a maximum after a latency of about 60 sec. Low concentrations of neurotensin (1-10 ng/mg) caused contraction, but at higher concentrations (50-1000 ng/ml) it produced a biphasic response which consisted of an initial contraction followed by a slow relaxation. In high tone preparations, the slow relaxation did not mimic the nerve-mediated response, taking approximately 43 sec. to reach maximum, after a long latency of about 15 sec. In contrast, ATP (0.1-50 microgram/ml) mimicked closely the rapid responses to non-adrenergic, non-cholinergic nerve stimulation in all preparations, whether the tone was low, medium or high. The time for the inhibitory response to reach maximum was about 15 sec after a latency of approximately 1 sec. Indomethacin (3.4-34 microgram/ml) did not unmask any inhibitory responses to any of the peptides. It is concluded that ATP remains the most likely substance to be the inhibitory transmitter released from non-adrenergic, non-cholinergic nerves supplying the smooth muscle of the taenia coli.
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PMID:Effects of neuronal polypeptides on intestinal smooth muscle; a comparison with non-adrenergic, non-cholinergic nerve stimulation and ATP. 42 25

The regulation of acid secretion was clarified by the development of H2-receptor antagonists in the 1970s. It appears that gastrin and acetylcholine exert their effects on acid secretion mainly by stimulation of histamine release from the enterochromaffin-like (ECL) cell of the fundic gastric mucosa. The isolated ECL cell of rat gastric mucosa responds to gastrin/cholecystokinin (CCK), acetylcholine, and epinephrine with histamine release and to somatostatin and R-alpha-methyl histamine by inhibition of histamine release. Histamine and acetylcholine stimulate the parietal cell by elevation of cAMP or [Ca]i by activation of H2 or M3 receptors, respectively. These independent pathways converge to activate the gastric acid pump, the H+,K+ ATPase. Activation is a function of the association of the ATPase with a potassium chloride transport pathway that occurs in the membrane of the secretory canaliculus of the parietal cell. Hence the secretory canaliculus is the site of acid secretion, the acid being pumped into the lumen of the canaliculus. The pump is composed of two subunits, a large catalytic and a smaller glycosylated protein. This final step of acid secretion has become the target of drugs also designed to inhibit acid secretion. The target domain of the benzimidazole class of acid pump inhibitors is the extracytoplasmic domain of the pump that is secreting acid, and the target amino acids are the cysteines present in this domain. The secondary structure of the pump can be analyzed by determining trypsin-sensitive bonds in intact, cytoplasmic-side-out vesicles of the ATPase, and it has been shown that the alpha subunit has at least eight membrane-spanning segments. Omeprazole, the first acid pump inhibitor, forms a disulfide bond with cysteines in the extracytoplasmic loop between the fifth and sixth membrane-spanning segment and to a cysteine in the extracytoplasmic loop between the seventh and eight segments, preventing phosphorylation of the pump by ATP. As a result of the effective and long-lasting inhibition of acid secretion by the acid pump inhibitor, superior clinical results have been found in all forms of acid-related disease.
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PMID:Acid secretion and the H,K ATPase of stomach. 134 Oct 65

Indirect evidence suggests that beta-1 adrenoceptors in the guinea pig ileum are innervated but it has not been determined whether "atypical" beta adrenoceptors also receive a postganglionic sympathetic innervation. To answer this question, experiments were undertaken using electrical stimulation of para-arterial sympathetic neurons to evoke relaxation in isolated segments of guinea pig ileum. Tension was developed in the ileal segments by either transmural electrical field stimulation to evoke the cholinergic "twitch" response, or by histamine to produce a steady-state contracture. Para-arterial sympathetic nerve stimulation evoked a frequency-dependent inhibition of the twitch response which was blocked by guanethidine and restored by dexamphetamine, indicating typical noradrenergic transmission. In preparations contracted with histamine and pretreated with benextramine to block alpha adrenoceptors, para-arterial sympathetic nerve stimulation evoked frequency-dependent relaxations which were reduced in magnitude but not abolished by the following beta adrenoceptor antagonists: bromoacetylalprenololmenthane (1 microM) or a combination of ICI 118,551 (0.3 microM) and CGP 20712A (0.1 microM). Remaining responses were blocked by compounds exhibiting affinity for atypical beta adrenoceptors, (-)-alprenolol (3 microM) and nadolol (300 microM), as well as the agonist (-)-isoproterenol (10 microM; to saturate the atypical beta adrenoceptor). However, relaxations to papaverine were unaffected by these treatments. Experiments revealed that potential cotransmitters (ATP, neuropeptide Y and somatostatin) do not appear to play a detectable role in relaxations produced by para-arterial sympathetic nerve stimulation. The results demonstrate, for the first time, that atypical beta adrenoceptors in guinea pig ileum receive a noradrenergic innervation.
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PMID:Evidence for a noradrenergic innervation to "atypical" beta adrenoceptors (or putative beta-3 adrenoceptors) in the ileum of guinea pig. 134 60

Somatostatin inhibition of growth hormone (GH) secretion from adenohypophysis cells in culture was antagonized by the antidiabetic sulfonylurea glipizide (K0.5 = 10 +/- 5 nM). Although all cells that hyperpolarize with somatostatin have ATP-sensitive K+ channels, the antagonistic actions of the hormone and of the antidiabetic drug are due to effects on different types of K+ channels. Diazoxide, an opener of ATP-sensitive K+ channels, abolished the increase of intracellular Ca2+ provoked by growth hormone releasing factor (GRF) and induced inhibition of GRF stimulated GH secretion (K0.5 = 138 microM). This inhibition by diazoxide was largely suppressed by glipizide which blocked the ATP-sensitive K+ channels opened by diazoxide. In summary, hormonal activation of GH secretion is inhibited by openers of ATP-sensitive K+ channels, while hormonal inhibition of GH secretion is suppressed by blockers of ATP-sensitive K+ channels.
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PMID:Effectors of ATP-sensitive K+ channels inhibit the regulatory effects of somatostatin and GH-releasing factor on growth hormone secretion. 135 34

The sulfonylurea glibenclamide, which is known to block ATP-sensitive potassium channels, increases, in a dose-dependent manner, the release of PRL from MMQ pituitary cells. Glibenclamide does not reduce the dopaminergic inhibition of forskolin-stimulated PRL secretion; conversely it almost completely abolishes the inhibitory effect of somatostatin (SRIF) on this parameter. The sulfonylurea dose dependently increases basal [Ca++]i, without affecting the increase in [Ca++]i induced by high concentrations of extracellular potassium. Glibenclamide does not modify dopamine-induced [Ca++]i reduction, whereas it abolishes the inhibitory effect of SRIF on basal [Ca++]i. In the presence of diazoxide, an opener of ATP-sensitive potassium channels, which lowers basal [Ca++]i, dopamine still reduces [Ca++]i whereas SRIF does not induce a further decrease. Glibenclamide induces the depolarization of the cell membrane and prevents the SRIF-evoked hyperpolarization. The hyperpolarization of the cell membrane induced by dopamine is not modified by glibenclamide. Diazoxide induces a cell membrane hyperpolarization that is enhanced by dopamine but not by SRIF. Finally, glibenclamide does not affect basal and stimulated adenylate cyclase activity. In conclusion, our findings show that, in MMQ cells, glibenclamide stimulates PRL release, suggesting an involvement of ATP-sensitive potassium channels in the regulation of PRL secretion. The reversal by glibenclamide of the effects of SRIF on calcium homeostasis, membrane potential, and PRL release suggests that this type of potassium channel participates to the somatostatinergic inhibition of PRL secretion. Conversely, we found that glibenclamide does not modify the dopaminergic inhibition of PRL secretion and second messenger systems, suggesting that ATP-sensitive potassium channels may not be involved in the inhibitory effect of dopamine on PRL release.
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PMID:Dopamine and somatostatin inhibition of prolactin secretion from MMQ pituitary cells: role of adenosine triphosphate-sensitive potassium channels. 135 54

Thyroid stimulating hormone (TSH) and other substances increase adenylate cyclase (AC) activity and growth of normal and neoplastic thyroid tissue. Factors that inhibit cAMP may provide targeted therapy to tumors dependent on cAMP for growth. Somatostatin has been reported to inhibit the growth of gastrinomas and carcinoid tumors. We therefore studied the effects of somatostatin on basal, TSH, pertussis toxin, and forskolin stimulated adenylate cyclase activity in normal and neoplastic thyroid tissue from 19 patients. Adenylate cyclase (AC) activity was determined by the conversion of alpha 32P-ATP to 32P-cAMP in pmoles/mg protein/30 minutes in an 8000 x g particulate fraction rich in thyroid plasma membranes. TSH (300 mU/ml) and forskolin (100 mM) (a diterpine that directly stimulates the catalytic unit of AC) increased AC activity in normal and neoplastic thyroid tissue. The AC stimulation was greater in the neoplasms (p less than 0.01). Somatostatin (5 x 10(-6)M) decreased basal and TSH stimulated AC activity below basal levels in both normal and neoplastic thyroid tissue (including papillary, follicular, and medullary carcinomas). The inhibition of AC by somatostatin was greater in neoplastic tissue (p less than 0.025). Pertussis toxin (which blocks the inhibitory guanyl nucleotide regulatory protein) was able to partially reverse the effect of somatostatin. Somatostatin partially inhibited forskolin stimulated AC activity. Somatostatin inhibits basal and TSH stimulated AC activity in both normal and neoplastic human thyroid tissue, with a greater effect on neoplasms. These studies establish that somatostatin blocks a major regulator of thyroid growth and provides the rationale for the use of somatostatin analogs in the treatment of thyroid cancers.
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PMID:Effect of somatostatin on adenylate cyclase activity in normal and neoplastic thyroid tissue. 135 26


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