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)

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.
 ...
PMID:Cyclic 3'5'-adenosine monophosphate and central circulatory control in cats and dogs. 2 Feb 56

The data presented concern the chemistry and biology of cardiotrop peptides and proteins isolated by us from the hypothalamus. The molecular mechanisms of the effect of neurohormone "C" (NC) as well as of a new cardiotrop hexapeptide from cattle hypothalamus are discussed. In in vitro studies on homogenates NC has been found to inhibit greatly not only 3'--5'-cyclo-AMP phosphodiesterase activity of brain and heart but also 3'--5'-cyclo-GMP phosphodiesterase activity. NC has been shown to be bound to specific proteins and to the regulatory unit of cyclo-AMP-dependent histone kinase of brain. It seems to compete with cyclo-AMP for the same proteins and is considered to be a regulator of intracellular cyclic nucleotides. NC has been shown to be combined to specific proteins in brain with non covalent bonds. A new cardiotrop hexapeptide has been shown to be present in bovine hypothalamus and its chemical structure has been found to be Tyr-Leu-Gly-Arg-Pro-Gly-amide. The acetylated form of this hexapeptide, which may be also present in brain, is much more active. The radioimmunochemical experiments carried out with antiserum 744 (from prof. Schally) by us have confirmed the existence of this hexapeptide and other fragments of LH-RH in the bovine hypothalamus. The effect of this hexapeptide on cardiac function and metabolism has been compared with a number of polypeptides (luliberin fragments). The hexapeptide has been shown to have not only cardiotropic but also a hypoglycaemic effect. It enhances the secretion of insulin and counteracts the inhibitory action of somatostatin on the insular apparatus. The hexapeptide produces significant changes in the activities of phosphorylase a and b as well as in that of phosphoprotein phosphatases. It reduces the amount of kinines in blood. Certain fractions of substance P, have been shown to have cardiotrop actitivty--they increase the rate of blood leaving the heart. The organotrop effects of a number of peptide neurohormones are discussed in connection with the hexapeptide. The results obtained have shown that the mechanisms underlying the effects of the cardioactive substances found by us are quite different. The data presented show that in brain a number of chemical factors (mainly peptides) are formed, which are involved in the regulation of heart function.
 ...
PMID:[Chemistry and biology of hypothalamic cardioactive proteins and peptides]. 22 93

We studied the interaction between somatostatin receptors and inhibitory GTP binding protein in rat cerebrocortical membranes. Guanine nucleotides reduced [125I-Tyr1] somatostatin binding to cerebrocortical membranes in a dose-dependent manner with rank order of potency being guanyl-5'-yl-imidodiphosphate (Gpp(NH)p) greater than GTP greater than GMP. Maximum reduction of the binding to 32% of control was observed in the presence of 10(-5) M Gpp(NH)p. Scatchard analysis of the labeled somatostatin binding revealed that the decrease in the binding by Gpp(NH)p was due to the decrease in the binding affinity for somatostatin. Divalent cations, such as Mg++, Mn++, and Ca++, caused an increase in labeled somatostatin binding to membranes with the maximum binding observed at a concentration of 10, 10, 1 mM, respectively. However, Na+ decreased a labeled somatostatin binding in a dose-dependent manner, and half maximum inhibition of the binding was observed at 10 mM Na+. Moreover, Gpp(NH)p and Na+ lowered labeled somatostatin binding in an additive fashion. When cerebrocortical membranes were treated at 37 degrees C for 40 min with various concentrations of Islet-Activating-Protein (IAP), which had been preactivated with dithiothreitol, subsequent labeled somatostatin binding to the membranes was decreased in a dose-dependent manner. 30 micrograms/ml IAP treatment caused a decrease in the binding to 50% of control, which was characterized by the decreased binding affinity without a significant change in the binding capacity. Furthermore, exposure of IAP plus NAD to cerebrocortical membranes caused ADP-ribosylation of a membrane protein with Mr = 41,000 on autoradiogram. Such an IAP treatment of cerebrocortical membranes abolished the inhibitory effect of somatostatin on vasoactive intestinal peptide-stimulated increase in adenylate cyclase activity. These results suggest that somatostatin receptors in the brain couple to inhibitory GTP binding protein, which mediates adenylate cyclase inhibition by somatostatin.
 ...
PMID:[Coupling of inhibitory GTP binding protein to somatostatin receptors on rat cerebrocortical membranes]. 257 11

To investigate whether somatostatin receptors couple to guanine nucleotide inhibitory protein, Ni, on rat pancreatic acinar membranes, the effects of guanine nucleotide analogs or pretreatment of acini with islet activating protein (IAP), pertussis toxin on labeled somatostatin binding were examined. Guanine nucleotides reduced labeled somatostatin binding to acinar membranes up to 80%, with rank order of potency being guanyl-5'-yl imidodiphosphate (Gpp(NH)p) greater than GTP greater than GDP greater than GMP. Scatchard analysis of the labeled somatostatin binding revealed that the decrease in somatostatin binding caused by Gpp(NH)p was due to the decrease in the maximum binding capacity without a significant change in the binding affinity. The inhibitory effect of Gpp(NH)p was partially abolished in the absence of Mg2+ and Na+ also reduced labeled somatostatin binding. Furthermore, inhibitory effects of 100mM Na+ and Gpp(NH)p were additive in reducing labeled somatostatin binding. A half maximal inhibitory concentration of Gpp(NH)p was decreased to 10(-7)M in the presence of 100mM Na+ and 5mM Mg2+ as compared to 10(-6)M in the presence of 5mM Mg2+ alone. Results therefore suggest that Gpp(NH)p requires Mg2+ for Ni activation and Na+ increases sensitivity of Ni to guanine nucleotide analogs. When pancreatic acini were treated for 4 hours with varying concentrations of IAP, which has been shown to uncouple Ni-mediated communication between inhibitory receptors and adenylate cyclase catalytic unit, subsequent labeled somatostatin binding to the acinar membranes was decreased in a dose dependent manner. These results indicate that somatostatin receptors on pancreatic acinar membranes couple to guanine nucleotide inhibitory protein, Ni and thus somatostatin probably functions in the pancreas to regulate intracellular signal transduction via Ni.
 ...
PMID:[Coupling of guanine nucleotide inhibitory protein to somatostatin receptors on rat pancreatic acinar membranes]. 282 26

Guanine nucleotides and pertussis toxin were used to investigate whether somatostatin receptors interact with the guanine nucleotide inhibitory protein (Ni) on pancreatic acinar membranes in the rat. Guanine nucleotides reduced 125I-[Tyr1]somatostatin binding to acinar membranes up to 80%, with rank order of potency being 5'-guanylyl imidodiphosphate [Gpp(NH)p] greater than GTP greater than GDP greater than GMP. Scatchard analysis revealed that the decrease in somatostatin binding caused by Gpp(NH)p was due to the decrease in the maximum binding capacity without a significant change in the binding affinity. The inhibitory effect of Gpp(NH)p was partially abolished in the absence of Mg2+. When pancreatic acini were treated with 1 microgram/ml pertussis toxin for 4 h, subsequent 125I-[Tyr1]somatostatin binding to acinar membranes was reduced. Gpp(NH)p further decreased somatostatin binding to islet-activating protein (IAP)-treated acinar membranes. Pertussis toxin treatment also abolished the inhibitory effect of somatostatin on vasoactive intestinal peptide-stimulated increase in cellular content of adenosine 3',5'-cyclic monophosphate (cAMP) in the acini. Furthermore, exposure of acini to IAP caused ADP ribosylation of a membrane protein with Mr = 41,000 in parallel to the inhibition of cAMP accumulation in acini. The present results suggest, therefore, that 1) somatostatin probably functions in the pancreas to regulate adenylate cyclase enzyme system via Ni, 2) the extent of modification of Ni is correlated with the ability of somatostatin to inhibit cAMP accumulation in acini, and 3) guanine nucleotides also inhibit somatostatin binding to its receptor.
 ...
PMID:Coupling of guanine nucleotide inhibitory protein to somatostatin receptors on pancreatic acinar membranes. 288 15

Acute intracerebral injection of the undecapeptide, substance P, in mice induced a unique reciprocal hindlimb scratching response whose intensity was dose-related. Similar intracerebral dose-response curves were obtained by the structurally related undecapeptides, physalaemin and eledoisin, but not by several unrelated peptides (TRH, neurotensin, bradykinin, somatostatin), prostaglandins E2 and F2a, dibutyryl cyclic AMP or dibutyrylcyclic GMP. Analgesic narcotic agents with predominant agonist activity administered i.p. prevented the reciprocal hindlimb scratching response induced by intracerebral substance P (0.625 microgram/mouse = ED 95). In this in vivo assay their action was stereospecific and exhibited a rank order of potency similar to that reported for analgesic activity and binding to opiate receptors in vitro. Narcotic agents with mixed agonist-antagonist activity were inactive while the narcotic antagonist, naloxone, completely reversed the action of morphine. Higher doses of naloxone alone potentiated substance P-induced reciprocal hindlimb scratching which may explain why partial narcotic agonists failed to abolish the response. There is now considerable evidence in support of a sensory neurotransmitter/modulator role for substance P within the central nervous system, and one of its actions may be associated with nociception. This concept is supported by observations in the present study which indicate that the substance P-induced reciprocal hindlimb scratching response involves nociceptive pathways within the central nervous system.
 ...
PMID:Intracerebral substance P in mice: behavioral effects and narcotic agents. 616 31

Natriuretic peptides inhibit the release and action of many hormones through cyclic guanosine monophosphate (cGMP), but the mechanism of cGMP action is unclear. In frog ventricular muscle and guinea-pig hippocampal neurons, cGMP inhibits voltage-activated Ca2+ currents by stimulating phosphodiesterase activity and reducing intracellular cyclic AMP; however, this mechanism is not involved in the action of cGMP on other channels or on Ca2+ channels in other cells. Natriuretic peptide receptors in the rat pituitary also stimulate guanylyl cyclase activity but inhibit secretion by increasing membrane conductance to potassium. In an electrophysiological study on rat pituitary tumour cells, we identified the large-conductance, calcium- and voltage-activated potassium channels (BK) as the primary target of another inhibitory neuropeptide, somatostatin. Here we report that atrial natriuretic peptide also stimulates BK channel activity in GH4C1 cells through protein dephosphorylation. Unlike somatostatin, however, the effect of atrial natriuretic peptide on BK channel activity is preceded by a rapid and potent stimulation of cGMP production and requires cGMP-dependent protein kinase activity. Protein phosphatase activation by cGMP-dependent kinase could explain the inhibitory effects of natriuretic peptides on electrical excitability and the antagonism of cGMP and cAMP in many systems.
 ...
PMID:Potassium channel stimulation by natriuretic peptides through cGMP-dependent dephosphorylation. 767 99

Nitric oxide synthase (NOS)-containing neurons are found in many loci throughout the central nervous system, which include the cerebral cortex, the cerebellum, the hippocampus, and the hypothalamus. NO plays a very important role in control of neuronal activity in all of these areas by diffusing into neurons where it activates soluble guanylate cyclase (sGC) leading to generation of cyclic guanosine monophosphate (cGMP) and cyclooxygenase 1 leading to generation of prostaglandins. Both of these active agents are involved in mediating the actions of NO, the first gaseous transmitter. In the cerebellum, NO is extremely important and it is also thought to mediate long-term potentiation in the hippocampus. Various stresses and corticoids have been shown in monkeys and also in rodents to cause neuronal cell death. This may be via the stimulation of glutamic acid release, which by N-methyl-D-aspartate (NMDA) receptors causes release of NO, which can lead to neuronal cell death. In the hypothalamus,. NO stimulates corticotropin-releasing hormone (CRH), prolactin releasing factor, growth hormone-releasing hormone (GHRH), and somatostatin, lutenizing hormone-releasing hormone (LHRH), but not follicle stimulating hormone-releasing factor (FSHRF) release. In situations of increased release of NO in the hypothalamus, it could cause neuronal cell death. Following bacterial or viral infections, toxic products of the ineffective agents, such as bacterial lipopolysaccharide (LPS), circulate to the brain, where they induce interleukin-1 and iNOS mRNA and synthesis. After several hours delay, massive quantities of NO are released. Induction of iNOS occurs in the choroid plexus, meninges, in circumventricular organs, and in large numbers of iNOS neurons in the arcuate and paraventricular nuclei. The large amounts of NO released by iNOS may well produce death not only of neurons but also glial. Repeated bouts of systemic infection even without direct neural involvement could result in induction of iNOS in the central nervous system and lead to large fall out of neurons in hippocampus to impair memory, hypothalamus to decrease fever, and neuroendocrine response to infection, and could play a role in the pathogenesis of degenerative neuronal diseases of aging, such as Alzheimers. The largest induction of iNOS occurs in the anterior pituitary and pineal glands. The damage to the pituitary could also impair responses to stress and infection, and the release of NO during infection could be responsible for the degenerative changes in the pineal and diminished release of melatonin, an antioxident, and consequently, an antiaging hormone, that occur with age.
 ...
PMID:The nitric oxide hypothesis of brain aging. 931 47

During infection, bacterial products, such as lipopolysaccharide (LPS), and viral products release cytokines from immune cells. These cytokines reach the brain by several routes. Furthermore, cytokines such as interleukin-1 (IL-1) are induced in central nervous system neurons by systemic injection of LPS. These cytokines determine the pattern of hypothalamic-pituitary secretion which occurs in infection. IL-2, by stimulation of cholinergic neurons, activates neural nitric oxide synthase (NOS). The nitric oxide (NO) released diffuses into corticotropin-releasing hormone (CRH)-secreting neurons and releases CRH. IL-2 also acts in the pituitary to stimulate adrenocorticotropic hormone secretion. On the other hand, IL-1 alpha blocks the NO-induced release of luteinizing-hormone-releasing hormone (LHRH) from neurons, thereby blocking pulsatile luteinizing hormone (LH), but not follicle-stimulating hormone release, and also inhibiting sexual behavior which is induced by LHRH. IL-1 alpha and granulocyte-macrophage colony-stimulating factor (GM-CSF) block the response of the LHRH terminals to NO. GM-CSF inhibits LHRH release by acting on its receptors on gamma-aminobutyric acid (GABA)ergic neurons to stimulate GABA release. GABA acts on GABA-A receptors on the LHRH neuronal terminal to block NOergic stimulation of LHRH release. This concept is supported by a blockade of GM-CSF-induced suppression of LHRH release from medial basal hypothalamic explants by the GABA-A receptor blocker, bicuculline. IL-1 alpha inhibits growth hormone (GH) release by inhibiting GH-releasing hormone release mediated by NO and stimulating somatostatin release, also mediated by NO. IL-1 alpha-induced stimulation of prolactin release is also mediated by intrahypothalamic action of NO which inhibits release of the prolactin-inhibiting hormone, dopamine. The actions of NO are brought about by its combined activation of guanylate cyclase liberating cyclic guanosine monophosphate and activation of cyclooxygenase and lipoxygenase, with liberation of prostaglandin E2 and leukotrienes, respectively. Thus, NO plays a key role in inducing the changes in the release of hypothalamic peptides induced in infection by cytokines. Cytokines, such as IL-1 beta, also act in the anterior pituitary gland, at least in part, via induction of inducible NOS. The NO produced alters the release of anterior pituitary hormones.
 ...
PMID:Nitric oxide controls the hypothalamic-pituitary response to cytokines. 948 1

During infection, bacterial and viral products, such as bacterial lipopolysaccharide (LPS), cause the release of cytokines from immune cells. These cytokines can reach the brain by several routes. Furthermore, cytokines, such as interleukin-1 (IL-1), are induced in neurons within the brain by systemic injection of LPS. These cytokines determine the pattern of hypothalamic-pituitary secretion which characterizes infection. IL-2, by stimulation of cholinergic neurons, activates neural nitric oxide synthase (nNOS). The nitric oxide (NO) released diffuses into corticotropin-releasing hormone (CRH)-secreting neurons and releases CRH. IL-2 also acts in the pituitary to stimulate adrenocorticotropic hormone (ACTH) secretion. On the other hand, IL-1 alpha blocks the NO-induced release of luteinizing hormone-releasing hormone (LHRH) from LHRH neurons, thereby blocking pulsatile LH but not follicle-stimulating hormone (FSH) release and also inhibiting sex behavior that is induced by LHRH. IL-1 alpha and granulocyte macrophage colony-stimulating factor (GMCSF) block the response of the LHRH terminals to NO. The mechanism of action of GMCSF to inhibit LHRH release is as follows. It acts on its receptors on gamma-aminobutyric acid (GABA)ergic neurons to stimulate GABA release. GABA acts on GABAa receptors on the LHRH neuronal terminal to block NOergic stimulation of LHRH release. This concept is supported by blockade of GMCSF-induced suppression of LHRH release from medial basal hypothalamic explants by the GABAa receptor blocker, bicuculline. IL-1 alpha inhibits growth hormone (GH) release by inhibiting GH-releasing hormone (GHRH) release, which is mediated by NO, and stimulating somatostatin release, also mediated by NO. IL-1 alpha-induced stimulation of prolactin release is also mediated by intrahypothalamic action of NO, which inhibits release of the prolactin-inhibiting hormone dopamine. The actions of NO are brought about by its combined activation of guanylate cyclase-liberating cyclic guanosine monophosphate (cGMP) and activation of cyclooxygenase and lipoxygenase with liberation of prostaglandin E2 and leukotrienes, respectively. Thus, NO plays a key role in inducing the changes in release of hypothalamic peptides induced in infection by cytokines. Cytokines, such as IL-1 beta, also act in the anterior pituitary gland, at least in part via induction of inducible NOS. The NO produced inhibits release of anterior pituitary hormones.
 ...
PMID:Role of nitric oxide in the neuroendocrine responses to cytokines. 962 49


1 2 Next >>