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. Acute effects of amino acids, hormones and drugs on transplantable rat insulinoma cells were examined after 2-3 days culture in RPMI-1640 (11.1 mM glucose) to eliminate necrotic cells and counter prior hypoglycaemia. 2. At 2.6 mM Ca2+, rat insulinoma cells (greater than 95% viability) released 48-97 ng insulin/10(6) cells during 60 min incubations with uptake of 1.0-1.8 nmol 45Ca/10(6) cells. 3. Insulin release and 45Ca uptake by rat insulinoma cells were not modified by arginine, leucine, 2-ketoisocaproate, tolbutamide, glibenclamide, somatostatin, adrenaline, noradrenaline, diazoxide or cyproheptadiene. 4. Responsiveness to acetylcholine (stimulation of insulin release and 45Ca uptake) and to GIP (stimulation of insulin release) was demonstrated. Thiol reagents (CMBS, CPDS and DTNB) and agents affecting microtubules-microfilaments (colchicine, vinblastine and cytochalasin B) enhanced insulin release. 5. The results suggest that rat insulinoma cells exhibit a generalized defect in the regulation of insulin release by nutrients, hormones and drugs which act in pancreatic B-cells by alteration of cellular Ca2+. Responsiveness to agents affecting insulin release through alternative mechanisms appears to be retained.
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PMID:Effects of amino acids, hormones and drugs on insulin release and 45Ca uptake by transplantable rat insulinoma cells maintained in tissue culture. 283 46

1. The spinal sympathetic outflow that innervates the gastrointestinal tract, including its blood vessels, has an impressive representation quantitatively, yet little is known about the functions of this system and its peripheral or central organization. Electrical stimulation or section of the splanchnic nerves have variable effects on the GI tract and does not, therefore, lead to a deeper understanding of the system. 2. The targets of the sympathetic supply of the GI tract are blood vessels, nonvascular (sphincteric) smooth musculature, myenteric neurones, submucous neurones and gut associated lymphoid tissues. The corresponding functions associated with these targets are regulation of blood flow (particularly through the mucosa) and resistance to flow, of motility, of secretion and absorption and of immune responses. Little is known about the effects of the sympathetic nervous system on the latter function. 3. The sympathetic postganglionic neurones are (at least in the guinea-pig) neurochemically characterized with respect to the targets. Neurones projecting to blood vessels contain neuropeptide Y in addition to noradrenaline, while neurones projecting to the submucous plexus contain somatostatin. No neuropeptide has been detected to date in neurones projecting to the myenteric plexus. 4. Transmission through guinea-pig prevertebral ganglia in vitro have been studied electrophysiologically. The following functions have been demonstrated: (a) transmission and distribution of preganglionic impulse activity to the targets in a relay-like fashion; (b) mediation of peripheral intestinointestinal reflexes between different sections of the GI tract; (c) integration of activity from the spinal cord and from various peripheral sources. The first function may apply particularly to the sympathetic pathway innervating blood vessels. Whether the second function occurs in vivo is questionable. The third function is the most important one for pathways involved in the regulation of motility and probably secretion and absorption. 5. Only limited information is available on preganglionic neurones projecting to prevertebral ganglia. Neurones regulating blood vessels are probably located in the intermediolateral cell column, and non-vascular visceral preganglionic neurones are situated medial to this cell column in the intermediate zone of the spinal cord. Vascular (vasoconstrictor) neurones exhibit a reflex pattern which is largely dependent on the brain stem. Spinal cord transection rostral to the sympathetic outflow causes an immediate abolition of basal and reflex activity in these neurones.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Integration of gut function by sympathetic reflexes. 283 10

1. The intracellularly-recorded electrical and mechanical responses to field stimulation of intramural nerves in three sympathetically-innervated smooth muscles--the mouse vas deferens, the rabbit ear artery and the rabbit mesenteric bed preparation were investigated. 2. In each tissue there was evidence for co-transmission involving noradrenaline (NA) and adenosine 5'-triphosphate (ATP) or a closely related nucleotide. 3. The electrical response in each tissue consisted of excitatory junction potentials (ejps) which were abolished by alpha, beta-methylene ATP (alpha, beta MeATP, 1-10 X 10(-6) M), suggesting that they were mediated by ATP. Only in the rabbit ear artery was there an additional electrical event mediated by NA. This took the form of a small slow membrane depolarization which followed the ejps and which was antagonized by either of the alpha-adrenoreceptor blocking agents phentolamine (1 X 10(-6) M) or prazosin (1 X 10(-7) M). 4. In the mouse vas deferens and rabbit mesenteric artery, both transmitter substances (NA and ATP) played a role in the contractile response to field stimulation. In the rabbit ear artery, NA alone appeared to mediate the contractile event. 5. Contractile responses to nerve-released ATP were accompanied by a membrane potential change, whereas those to NA appeared to be mediated largely by a voltage-independent mechanism. 6. In the mouse vas deferens, the ejps and action potentials evoked by field stimulation appeared to be mediated by a discrete increase in permeability to Na+ and K+. 7. In the mouse vas deferens, local application of bradykinin (1-100 X 10(-7) M) produced a small, slow membrane hyperpolarization. VIP (1-100 X 10(-7) M), neuropeptide Y (1-100 X 10(-7) M), substance P (1-100 X 10(-7) M), somatostatin (1-100 X 10(-7) M), leu-enkephalin (1-100 X 10(-7) M), metenkephalin (1-100 X 10(-7) M) and bombesin (1-100 X 10(-7) M), similarly applied, each produced no significant change in membrane potential. None of these peptides appear to be the transmitter mediating the ejp in this tissue.
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PMID:The electrical and mechanical basis of co-transmission in some vascular and non-vascular smooth muscles. 284 46

1. Intracellular recordings of membrane potential and current were made from neurones in the lateral parabrachial nucleus in slices of rat brain in vitro. 2. The membrane was hyperpolarized by the opioid peptides Tyr-D-Ala-Gly-MePhe-Gly-ol (DAGOL, 0.01-1 microM) and [Met5]enkephalin (3-30 microM), though not by Tyr-D-Pen-Gly-Phe-D-Pen and U50488. In two experiments, naloxone competitively antagonized the effects of DAGOL and [Met]enkephalin with equilibrium dissociation constants of 0.8 and 3.2 nM, respectively. 3. Baclofen (0.3-30 microM) also hyperpolarized the neurones; this action was unaffected by naloxone. 4. DAGOL, [Met5]enkephalin and baclofen caused outward currents at the resting potential. These currents reversed polarity at a membrane potential which changed with the logarithm of the extracellular potassium concentration. 5. Muscarine has been shown previously to increase the potassium conductance by an action at M2-receptors: the potassium currents induced by maximal concentrations of muscarine, baclofen and [Met5]enkephalin were non-additive, indicating that these agonists opened the same population of potassium channels. 6. Noradrenaline, UK14304, carboxamidotryptamine, dopamine, adenosine and somatostatin had little or no effect on membrane potential. 7. It is concluded that rat lateral parabrachial neurones express mu-opioid, gamma-aminobutyric acidB (GABAB), and M2-muscarinic receptors: activation of any of these receptors increases the potassium conductance of the membrane and inhibits the neurones through hyperpolarization.
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PMID:Agonists at mu-opioid, M2-muscarinic and GABAB-receptors increase the same potassium conductance in rat lateral parabrachial neurones. 285 64

Senile dementia of the Alzheimer's type can be diagnosed with certainty only by examining neurofibrillary tangles and neuritic plaques under the microscope. Recently, it has been suggested that the condition is linked to specific neurotransmitter systems, with a decline of cortical acetylcholine, choline acetyltransferase, cholinergic neurones projecting to the cortex, cortical noradrenaline content, locus coeruleus neurones and cortical somatostatic content. Using immunocytochemical methods, we here report that somatostatin-immunoreactive processes are present in neuritic plaques in human Alzheimer's specimens. These data, as well as other reports of non-cholinergic changes, strongly imply that Alzheimer's disease cannot be linked exclusively to cortical cholinergic elements, as proposed previously. Rather, our data on plaque and somatostatin co-localization and distribution patterns suggest that Alzheimer's neuropathology may involve primarily the loss of selective cortical neurones that are targets of the implicated transmitter systems and that plaque formation may result from the degeneration of presynaptic and postsynaptic neurites of large projection neurones in layers III and V. Given the neurochemically heterogeneous input to these cells, it is not surprising that several neurotransmitter systems, one of which is somatostatin, are implicated in the pathology of Alzheimer's disease.
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PMID:Somatostatin immunoreactivity in neuritic plaques of Alzheimer's patients. 285 56

Neuropeptide Y-like immunoreactivity (NPY-LI) was enriched in synaptosomal fractions of neocortex, which on lysis yielded vesicle-rich fractions. The distribution of NPY-LI on a sucrose density gradient was similar to that of somatostatin, with a concentration in heavy vesicles. The peptides were not found in light vesicles in contrast to the distribution of noradrenaline. Both homogenate and vesicular NPY-LI coeluted with synthetic NPY on reverse-phase HPLC.
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PMID:Subcellular distribution of neuropeptide Y-like immunoreactivity in guinea pig neocortex. 286 Sep 47

The neuropeptide somatostatin potentiates beta-adrenergic receptor-mediated cAMP formation in astrocytes derived from neonatal rat cortex but does not affect cAMP levels by itself. beta-Adrenergic receptors in these cells can be specifically labeled with the high affinity antagonist [125I] cyanopindolol ([125I]CYP). In addition, astrocytes display both high and low affinity binding sites for the agonist isoproterenol, which are thought to represent receptors which are coupled or uncoupled, respectively, to the guanine nucleotide regulatory protein. We find that somatostatin does not modify beta-receptor density, nor receptor affinity for either the antagonist ([125I]CYP) or for the agonist isoproterenol. In the presence of the guanine nucleotide analogue, Gpp(NH)p, only low affinity (uncoupled) displacement of [125I]CYP binding by isoproterenol is observed. However, somatostatin (1 microM), when added to the cells together with Gpp(NH)p, prevents the nucleotide-induced loss of the high affinity (coupled) component of agonist displacement. This result suggests that somatostatin increases noradrenaline-induced cAMP production by enhancing coupling between the beta-receptor and the stimulatory guanine nucleotide regulatory protein.
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PMID:Somatostatin alters beta-adrenergic receptor-effector coupling in cultured rat astrocytes. 286 27

Alzheimer's disease (AD) and senile dementia (SD) are often classified together, but there are genetic, biochemical, neuropathological and clinical arguments for separating them. The well-known Alzheimer lesions in the brains of patients with AD and SD are described, as is the loss of neurons in the locus coeruleus. White matter changes in brains from patients with dementia are discussed and related to AD and SD. Biochemical changes in brains of patients with AD and SD include reduced activity of acetylcholinesterase (AChE) and choline-acetyltransferase (CAT), indicating reduced activity in the acetylcholinergic system. There is also, however, reduced activity in the dopamine (DA), noradrenaline (NA) and 5-hydroxytryptamine (5-HT) system. The active amines are decreased while the end metabolites are decreased to a lesser extent or normal. The levels of the active amines are thought to reflect the number of neurons, while the levels of end metabolites reflect the rate of turnover in the system. 3-Methoxy-4-hydroxyphenylglycol (MHPG) is increased to levels above normal, which may indicate an increased rate of turnover in the NA system. Monoamine oxidase B (MAO-B), which is increased in advanced age, is further increased in patients with AD and SD. It is assumed that this enzyme is localized in extraneuronal tissue, and therefore the increase may reflect a gliosis. In brains from patients with AD and SD neuropeptides are also studied. Only somatostatin and substance P, however, seem to be reduced, indicating selective damage to the neuropeptides. The biochemical changes can be given pathogenetic importance.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Alzheimer's disease and senile dementia: biochemical characteristics and aspects of treatment. 286 36

The effect of chemical stimulation of the brain on glucoregulation was studied in anaesthetized rats. Adrenaline, noradrenaline, acetylcholine, dopamine and carbachol (5 X 10(-8) mol/microliter saline) were injected directly into the third cerebral ventricle and changes in hepatic venous plasma glucose, immunoreactive glucagon and insulin concentrations were studied. The injection of adrenaline and carbachol into the third cerebral ventricle resulted in a marked hyperglycaemia associated with increased immunoreactive glucagon. Adrenaline-induced hyperglycaemia was not affected by bilateral adrenalectomy, while carbachol-induced hyperglycaemia was completely inhibited by adrenalectomy. The injection of somatostatin (1 X 10(-9) mol) with adrenaline into the third cerebral ventricle did not influence adrenaline-induced hyperglycaemia, while carbachol-induced hyperglycaemia was inhibited by co-administration with somatostatin. These results suggest that adrenergic and cholinergic neurons in the central nervous system may increase hepatic glucose output by different mechanism.
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PMID:Central hyperglycaemic effect of adrenaline and carbachol. 286 11

To examine the beta-adrenergic effects of the catecholamines in poorly controlled diabetes, we have studied insulin-deprived alloxan-diabetic (A-D) dogs during 90 min of moderate exercise (100 m/min, 10-12 degrees) alone (C) or with propranolol (5 micrograms . kg-1 . min-1) (P) or combined P and somatostatin infusion (0.5 microgram . kg-1 . min-1) (P + St). In P, in contrast to C, immunoreactive glucagon (IRG) rose only after 50 min of exercise. However, hepatic glucose production (Ra) rose normally. In P + St, IRG fell 50% below basal, and the Ra response to exercise was abolished. Interestingly, in P and P + St, glucose metabolic clearance rate (MCR) rose by 400% above the inadequate MCR response to exercise in C, despite 30% lower insulin levels. Compared with C, free fatty acids (FFA) and lactate were sharply reduced during P and P + St. Plasma glucose (G) did not change in C, but due to elevated glucose uptake, G fell over 120 mg/dl in P, and due to diminished Ra, G fell 170 mg/dl in P + St. Norepinephrine was similar in all groups. Epinephrine and cortisol were higher in P + St by 90 min of exercise, perhaps as a result of hypoglycemia. In summary, during exercise in poorly controlled A-D dogs, beta-blockade does not appear to affect Ra; beta-blockade leads to diminished mobilization of extrahepatic substrate as evidenced by reduced FFA and lactate levels; beta-blockade increases MCR to levels seen in normal dogs during exercise alone.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Role of beta-adrenergic mechanisms during exercise in poorly controlled diabetes. 286 46


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