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

Receptors for the main neural (acetylcholine), hormonal (gastrin) and paracrine (histamine) secretory stimulants and the signal transduction pathways to which these receptors are coupled have been identified on the parietal cell. The stimulatory effect of histamine is mediated via an increase in adenylate cyclase activity, whereas the effect of acetylcholine and gastrin are mediated via an increase in cytosolic levels of calcium. Strong synergism between histamine and either gastrin or acetylcholine may reflect postreceptor interaction between the distinct pathways. Acetylcholine and gastrin are also capable of releasing histamine from the gastric mucosa, probably from ECL cells. The inhibitory effects of somatostatin and prostaglandin E on acid secretion are mediated by receptors coupled via guanine nucleotide binding proteins to inhibition of adenylate cyclase activity. All the pathways converge on and modulate the activity of the luminal enzyme, H+K(+)-ATPase, ultimately responsible for acid secretion. The intramural neural and paracrine pathways involved in the regulation of gastrin secretion in the antrum and acid secretion in the fundus have also been identified. Of prime importance is the somatostatin cell, which exerts a paracrine restraint on gastrin secretion and acid secretion. Elimination of this restraint or disinhibition is one of the mechanisms by which the stimulatory influence of cholinergic neurons is exerted on gastrin and parietal cells. Gastrin secretion is regulated by a cholinergic neuron that causes inhibition of somatostatin secretion and thus stimulation of gastrin secretion (disinhibition) and a noncholinergic neuron that causes direct stimulation of gastrin secretion by releasing the neurotransmitter, bombesin (or gastrin-releasing peptide). Acid secretion is regulated by a cholinergic neuron that causes direct stimulation of the parietal cell and indirect stimulation by decreasing somatostatin secretion, thus eliminating its inhibitory effect on the parietal cell (disinhibition). In addition, a regulatory feedback mechanism exists whereby intraluminal acidification stimulates somatostatin secretion, which in turn attenuates acid secretion. Gastric acid secretion may also be regulated by one or more intestinal inhibitory hormones, the most likely candidates being secretin, intestinal somatostatin, and neurotensin. Enterogastrone activity probably reflects the combined effect of all these hormones. Precise information on receptors and signal transduction mechanisms as well as on intramural neural and paracrine regulatory pathways has led to the development of new drugs capable of inhibiting acid secretion. These include antagonists that interact with stimulatory receptors (histamine H2-receptor antagonists, muscarinic receptor antagonists, and gastrin receptor antagonists), agonists that interact with inhibitory receptors (somatostatin and prostaglandin E analogues), and irreversible inhibitors of the luminal enzyme, H+K(+)-ATPase.
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PMID:Control of acid secretion. 169 38

Enzymatically isolated rat gastric mucosal cells (0.25% G-cells) were separated by counterflow elutriation, yielding a fraction in which the G-cell content was relatively enriched to 1.4%. In this fraction, basal gastrin release (mean +/- SE) was 31.1 +/- 1.3 pg.10(6) cells-1.60 min-1 and was stimulated by 10(-8) M neuromedin C (222.3 +/- 18.1% of basal), 10(-4) M carbachol (227.5 +/- 25.9%), 10(-6) M 12-O-tetradecanoylphorbol-13-acetate (TPA) (196.3 +/- 14.7%), and 10(-3) M dibutyryl adenosine 3',5'-cyclic monophosphate (DBcAMP) (193.9 +/- 6.8%), respectively. The neuropeptide galanin was tested at 10(-10) to 10(-7) M. Galanin had no effect on basal gastrin release but reduced the responses to neuromedin C, carbachol, TPA, and DBcAMP. IC50 ranged between 1 X 10(-10) and 8.6 X 10(-10) M galanin. Although in the relatively enriched G-cell fraction D-cells were not detectable by immunocytochemistry, a low rate of somatostatin release was still measured by radio-immunoassay (5.3 +/- 0.5 pg.10(6) cells-1.60 min-1). However, galanin failed to increase this rate under basal conditions or in response to any of the stimulants tested. These results favor the assumption that galanin might exert a direct inhibitory effect on rat gastric G-cells. Galanin seems to interfere at an intracellular mechanism(s), which is induced by neuromedin C and carbachol and which is commonly activated by protein kinase C- and cAMP-mediated stimulation.
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PMID:Galanin inhibits gastrin release from isolated rat gastric G-cells. 169 87

An immunocytochemical investigation was carried out on round and spreading hemocytes of Planorbarius corneus by using 20 antisera to vertebrate bioactive peptides. The immunotests showed the presence of alpha 1-antichymotrypsin-bombesin-, calcitonin-, CCK-8 (INC)-, CCK-39-, gastrin-, glucagon-, Met-enkephalin-, neurotensin-, oxytocin-, somatostatin-, substance P-, VIP-, and vasopressin-immunoreactive molecules in the spreading hemocytes. The round hemocytes were only positive to anti-bombesin, anticalcitonin, anti-CCK-8 (INC), anti-CCK-39, anti-neurotensin, anti-oxytocin, anti-substance P and anti-vasopressin antibodies. No immunostaining was observed with anti-CCK-8 (Peninsula), anti-insulin, anti-prolactin, anti-thyroglobulin and anti-thyroxin (T4) antibodies. As probably in vertebrates, these bioactive peptides may modulate immuno cell function.
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PMID:Immunocytochemical evidence of vertebrate bioactive peptide-like molecules in the immuno cell types of the freshwater snail Planorbarius corneus (L.) (Gastropoda, Pulmonata). 169 11

The effects of the brain-gastrointestinal polypeptide neurotransmitters bombesin, substance P, neurotensin, and somatostatin-14 on cytotoxicity of peripheral blood mononuclear cells against K-562 and CaCo-2 tumour cells were investigated. Bombesin significantly stimulated cytotoxicity against CaCo-2 target cells (10(-12), 10(-10) M and 10(-6) M) and against K-562 target cells (10(-12) and 10(-10) M) in the short 4 hour assay. Substance P showed a tendency to stimulate cytotoxicity at higher concentrations but the changes observed did not reach significance because of large inter-individual variation of responsiveness. Neurotensin did not influence cytotoxicity against either target cell lines. Somatostatin was found to have no influence on cytotoxicity of peripheral blood mononuclear cells but was the only peptide tested which markedly increased chromium release by target cells alone. These findings support the idea that brain-gastrointestinal neuropeptides can play a part in tumour cytotoxicity.
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PMID:Neuropeptide regulation of cell-mediated cytotoxicity against human tumor cells. 170 Dec 25

Immunohistochemical methods were used to determine the localisation of immunoreactivities to a variety of antigens involved in neurotransmission in the myenteric plexus of the colon in the rat and mouse. The findings in the two species were closely similar. Five neuronal types have been identified. (i) The axons of extrinsic noradrenergic sympathetic neurons, immunoreactive for tyrosine hydroxylase, supply the ganglia and the circular muscle. (ii) Bombesin immunoreactive intrinsic neurons with unbeaded axons are largely confined to the ganglia and tracts of the plexus. These neurons probably contain gastrin-releasing peptide, which is the mammalian analogue of bombesin. (iii) Somatostatin immunoreactive intrinsic neurons have long, beaded axons within the myenteric plexus and also outside the plexus, between the longitudinal and circular muscle layers. (iv) Intrinsic neurons containing opioid peptides (beta-endorphin, met-enkephalin, leu-enkephalin), have beaded axons that cannot be traced for long distances. They contact all the cell bodies in the ganglia and extend also into the interganglionic tracts and the smooth muscle. (v) Substance P immunoreactive somata and axons are present throughout the myenteric plexus and provide dense innervation to the smooth muscle. Extrinsic substance P immunoreactive sensory axons are probably also present.
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PMID:An immunohistochemical study of the myenteric plexus of the colon in the rat and mouse. 170 22

N-terminal fragments of substance P (SP) were tested for antagonism against the aversive responses induced in mice by various tachykinin receptor agonists, somatostatin and bombesin. When co-administered with SP intrathecally, low doses (1.0-4.0 pmol) of SP (1-7) or SP (1-8) reduced the SP-induced behavioural responses of scratching, biting and licking. Aversive responses induced by two other neurokinin (NK) 1 receptor agonists, Septide and physalaemin, were also dose-dependently decreased by the simultaneous injection of small doses of SP (1-7) or SP (1-8). Aversive responses induced by 400 pmol of NK A were also significantly reduced by co-administration of SP (1-7) or SP (1-8). No significant effects of the N-terminal fragments were observed against the aversive responses elicited by NK A (300 pmol), eledoisin, NK B, somatostatin or bombesin. These results suggest that the behavioural antagonism produced by SP (1-7) and SP (1-8) may be limited to the NK 1 receptor at the spinal level in mice.
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PMID:N-terminal substance P fragments inhibit the spinally induced, NK 1 receptor mediated behavioural responses in mice. 170 44

Central and lateral hypothalamic concentrations of 9 regulatory peptides implicated in the control of feeding behaviour were measured in corpulent (cp/cp) JCR:LA-cp rats which develop spontaneous obesity, hyperinsulinaemia and hyperlipidaemia, and in lean (+/?) controls. In female cp/cp rats, central hypothalamic levels of neuropeptide Y (NPY), neurotensin, somatostatin and substance P were significantly lower (p less than 0.02) than in lean female controls. Following food restriction with a 16% reduction in body weight, these differences were apparently reversed and there were also significant rises in the lateral hypothalamic concentrations of neurotensin and of galanin. The other 4 peptides examined (bombesin, calcitonin gene-related peptide, neuromedin B and vasoactive intestinal peptide) did not differ significantly between cp/cp and lean females, either fed freely or food-restricted. Male cp/cp rats showed no significant differences from lean males in central or lateral hypothalamic concentrations of any of the 9 peptides. NPY and galanin are powerful and specific central appetite stimulants, whereas neurotensin, substance P and somatostatin inhibit feeding when injected centrally. Disturbances in these putative appetite-regulating peptides may be involved in the hyperphagia and other hypothalamic abnormalities in this spontaneous obesity syndrome. The apparent absence of differences between the male corpulent and lean groups may relate to sexual dimorphism of the syndrome, which is more marked in the females.
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PMID:Hypothalamic regulatory peptide disturbances in the spontaneously obese JCR: LA-corpulent rat. 172 Mar 64

The distribution of basic fibroblast growth factor (bFGF)-immunoreactivity (IR) was studied in rat sensory and autonomic ganglia. In postnatal and adult sympathetic superior cervical ganglia and in adult parasympathetic otic ganglia no bFGF-staining was found. Postnatal and adult neural crest- and placode-derived sensory ganglia displayed intensive bFGF-IR in a neuronal subpopulation. This subpopulation was characterized by use of consecutive sections of adult dorsal root ganglia stained with antibodies against substance P, somatostatin, bombesin, and bFGF. Basic FGF was colocalized with the somatostatin/bombesin subpopulation but not with substance P.
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PMID:Localization of basic fibroblast growth factor in a subpopulation of rat sensory neurons. 173 9

The effect of bombesin against injury on rat islet B cells was studied in three kinds of experiments: (1). In vivo experiment, it was found that preinjection of bombesin (50 micrograms/kg, sublingual v.) could effectively prevent an increase of plasma glucose and decrease of plasma insulin in diabetic rat induced by alloxan (200 mg/kg, s.c.) (2). In vitro experiment, isolated pancreas perfusion showed that alloxan-induced (14 mmol/L) perfusion fluid inhibition of insulin secretion could be reversed by pretreatment of bombesin (10(-3) mmol/L). (3). Investigation on isolated and incubated islets demonstrated that alloxan induced decrease of insulin and somatostatin secretion and increase of glucagon secretion could be prevented by bombesin. The above-mentioned results suggest that bombesin may play an important role in the regulation of plasma glucose in diabetic rat and have a potent preventive effect against the development of diabetes.
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PMID:[Preventive effect of bombesin on alloxan-induced diabetes in rat]. 179 6

To determine whether CNS regulatory pathways are organized so that differential sympathetic outflow patterns occur in response to stress, we injected various doses of neostigmine or bombesin into the third cerebral ventricle of fed rats, and then measured the hepatic venous plasma concentrations of glucose, glucagon, insulin, and epinephrine. The following four groups of rats were studied. Group 1 was intact rats. Group 2 comprised intact rats receiving the constant infusion of a) somatostatin to inhibit the endogenous secretion of insulin and glucagon, and b) insulin to maintain the plasma insulin concentration at basal levels. The infusion was started from -30 minutes and given via a catheter in the femoral vein. Group 3 consisted of rats that underwent bilateral adrenal medullectomy (ADMX) one week before the experiment. Group 4 was ADMX rats administered a constant infusion of somatostain with insulin through a femoral vein, as above. The administration of 1 x 10(-9) mol neostigmine caused hepatic venous hyperglycemia mediated by three distinct pathways: 1) direct innervation of the liver, 2) a direct action of epinephrine on the liver, and 3) the action of glucagon on the liver. We estimated the relative contribution of these three factors to be about 47, 32, and 21%, respectively. Relative contributions of three factors of the doses of 5 x 10(-9) and 5 x 10(-8) mol neostigmine demonstrated an effect similar to that of 1 x 10(-9) mol neostigmine. Epinephrine was shown to be the only agent involved in the hyperglycemic response to intraventricular bombesin at doses of 1 x 10(-10), 1 x 10(-9), and 1 x 10(-8) mol.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Relative contribution of nervous system and hormones to CNS-mediated hyperglycemia is determined by the neurochemical specificity in the brain. 180 63


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