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. Whole-cell recordings were made from submucosal neurones acutely dissociated from guinea-pigs. The actions of noradrenaline, somatostatin and [Met5]enkephalin on currents carried by calcium ions were studied. 2. On depolarization from a holding potential of -70 mV, an inward current activated at -40 mV, reached its peak amplitude at 10 mV and reversed to outward at 72 mV (with external calcium of 5 mM and internal caesium of 160 mM). 3. Cadmium, nickel and cobalt reversibly blocked the calcium current; concentrations causing 50% block were 2.5, 500 and 2000 microM respectively. The calcium current (holding at -70 or -30 mV) was reversibly blocked by omega-conotoxin (100 nM), and unaffected by Bay K 8644 (0.1-10 microM) and nifedipine (1 microM). Cadmium caused an outward shift in holding current at -30 mV, implying that there was a persistent inward calcium current at this potential. 4. Noradrenaline, somatostatin and [Met5]enkephalin decreased the calcium current. The maximal inhibition observed with any one agonist, or with a combination of two agonists, did not exceed 50%; concentrations giving half-maximal inhibition were 5.5 microM for noradrenaline, 4 nM for somatostatin and 1 microM for [Met5]enkephalin. The inhibition was independent of membrane potential. All three agonists also reduced the persistent calcium current at -30 mV. 5. Inhibition of the calcium current by noradrenaline occurred with a latency of not less than 175 ms; cadmium applied by the same method depressed the current within 5-45 ms. 6. Experiments with selective agonists and antagonists indicated that the receptor types involved in calcium current inhibition were alpha 2-adrenoceptors and delta-opioid receptors. Somatostatin acted at a distinct receptor. 7. Calcium currents were also inhibited by intracellular dialysis with guanosine 5'-O-(3-thiotriphosphate) (GTP-gamma-S). Agonists were ineffective in cells pre-treated with pertussis toxin, but their action was restored when purified GTP-binding proteins (Go or Gi) were included in the intracellular recording solution. 8. It is concluded that noradrenaline, somatostatin and [Met5]enkephalin act at their respective receptors on guinea-pig submucosal neurones to inhibit a voltage-dependent calcium current. Activation of the same receptors also increases a potassium conductance in these cells: in both cases a pertussis-sensitive G protein is involved.
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PMID:Inhibition of calcium currents by noradrenaline, somatostatin and opioids in guinea-pig submucosal neurones. 198 21

In this study, we characterize the glucagon receptors on rat retinal particulate preparations. The specific binding of 125I-glucagon was saturable and reversible. Apparent equilibrium conditions were established within 30-45 min. Analysis of binding data is compatible with the existence of two classes of binding sites: a high-affinity class with a KD of 7 +/- 0.8 nM and a Bmax of 2.3 +/- 0.2 pmol/mg of protein and a low-affinity class with a KD of 84.4 +/- 2.5 nM and a Bmax of 16.5 +/- 2.3 pmol/mg of protein. The 125I-glucagon binding to retinal particulate preparation was not inhibited by 1 microM concentrations of insulin, atrial natriuretic factor, angiotensin II, somatostatin, and vasoactive intestinal peptide. However, synthetic human pancreatic growth hormone-releasing factor, hGRF-44, inhibited binding, although the concentration required for half-maximal displacement was 10-fold higher than that for native glucagon. Glucagon binding was GTP sensitive. Inclusion of 0.1 mM GTP in the binding assay produced an increase in the concentration of unlabeled glucagon required for half-maximal displacement of 125I-glucagon, from 23 to 220 nM. Glucagon stimulated adenylate cyclase formation in retinal particulate preparations. The concentration of glucagon required for half-maximal activation of retinal adenylate cyclase was 16.2 nM. These results suggest that glucagon may play a role as a neurosignal transmitter in rat retina.
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PMID:Identification of glucagon receptors in rat retina. 215 17

We have previously determined that beta-adrenergic and somatostatin receptors stimulate and inhibit, respectively, Na-H exchange independent of changes in cAMP accumulation (Barber, D.L., McGuire, M.E., and Ganz, M.B. (1989) J. Biol. Chem. 264, 21038-21042). The present study extends our work on the beta-adrenergic receptor (beta AR) by investigating receptor activation of Na-H exchange in multiple cell types that either endogenously express the beta AR or that have been transfected with cDNA of the hamster lung beta 2AR or the turkey erythrocyte beta AR. Exchanger activity was determined by monitoring intracellular pH in cell populations loaded with the pH-sensitive dye BCECF (2,7-biscarboxyethyl-5(6)-carboxyfluorescein). In addition to the action of the beta AR, activation of prostaglandin E1 and parathyroid hormone receptors induced an intracellular alkalinization by stimulating a Na(+)-dependent amiloride-sensitive Na-H exchange. In contrast, activation of D2-dopaminergic receptors induced an intracellular acidification by inhibiting Na-H exchange. beta-Adrenergic, prostaglandin E1, and parathyroid hormone receptors activated Na-H exchange independent of changes in intracellular cAMP accumulation and independent of a cholera toxin-sensitive stimulatory GTP regulatory protein. D2-dopaminergic receptors inhibited exchanger activity independent of a pertussis toxin-sensitive inhibitory GTP regulatory protein. We suggest that these receptors are functionally coupled to adenylate cyclase and Na-H exchange through divergent signaling mechanisms.
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PMID:Multiple receptors coupled to adenylate cyclase regulate Na-H exchange independent of cAMP. 216 Sep 51

Somatostatin (SRIF) induces its biological actions by binding to and stimulating membrane-associated receptors. To investigate the molecular mechanisms by which SRIF induces its biological effects, we have characterized the biochemical properties of SRIF receptors. SRIF receptors can be solubilized in an active form with the detergent CHAPS and can be detected with the high-affinity SRIF analog [125I]MK 678. The pharmacological characteristics of solubilized SRIF receptors from brain are similar to the receptors in membranes, suggesting that the solubilized receptors retain their biological activity. Solubilized SRIF receptors appear to be tightly associated with GTP-binding proteins, since analogs of GTP can greatly reduce agonist labeling of the solubilized SRIF receptor. The solubilized SRIF receptor migrates as a mass of approximately 400 kd and is a glycoprotein since it can specifically interact with lectin columns. The solubilization of the SRIF receptor has allowed for its purification by affinity chromatography. The purified SRIF receptor migrates as a mass of 60 kd in denaturing gels. Using affinity chromatography, the receptor can be purified to near homogeneity. Present studies are directed toward sequencing and cloning cDNA encoding the SRIF receptor in order to further characterize its physical properties and expression.
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PMID:Biochemical properties of somatostatin receptors. 216 74

G proteins couple receptors to ionic channels indirectly by acting on membrane enzymes which modulate channel activity through second or third messengers such as cytoplasmic kinases, IP3 or Ca++. Recently, it has been shown that G proteins can act on ionic channels in a membrane-delimited or direct manner; from our experience this phenomenon seems to be widespread. A G protein purified from human red blood cells (hRBC) Gk when preactivated with GTP gamma S acts directly on muscarinic acetylcholine receptor-regulated K+ channels (K+[ACh]) in atrial cells and the stimulatory regulator of adenylyl cyclase, Gs from hRBCs acts directly on two distinct voltage-gated Ca++ channels, one in cardiac muscle and the other in skeletal muscle T-tubules. In many cells, including clonal GH3 pituitary cells, somatostatin (SST) inhibits secretion by a complex mechanism that involves a pertussis toxin (PTX)-sensitive step. This is not due to lowering cAMP since secretion induced by cAMP analogs and K+ depolarization are also inhibited. SST also causes membrane hyperpolarization, which is similar to the effect of ACh on cardiac pacemaking cells and may lead to decreases in intracellular Ca++ needed for secretion. ACh acting through a muscarinic recpetor in GH3 cells has the same effects as SST.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Direct coupling of the somatostatin receptor to potassium channels by a G protein. 216 76

Somatostatin reduces voltage-dependent Ca2+ current (ICa) and intracellular free Ca2+ concentration in the AtT-20/D16-16 pituitary cell line. We tested whether guanine nucleotide-binding proteins (G or N proteins) are involved in the signal transduction mechanism between the somatostatin receptor and voltage-dependent Ca2+ channels. Treatment of the cells with pertussis toxin, which selectively ADP ribosylates the GTP binding proteins Gi and Go and suppresses the ability of Gi to couple inhibitory receptors to adenylate cyclase, abolished the action of somatostatin on both ICa and intracellular free Ca2+. Intracellular application of the nonhydrolyzable guanine nucleotide analog guanosine 5'-[gamma-thio]triphosphate (GTP[gamma S]), which irreversibly activates G proteins, changed the somatostatin effect on ICa from a reversible to an irreversible inhibition. Intracellular GTP[gamma S] alone caused a very slowly developing inhibition of ICa. When ICa was inhibited by GTP[gamma S] (alone or with somatostatin), it failed to respond to subsequent applications of somatostatin. The effect of GTP[gamma S] on the inhibition of ICa by somatostatin was not altered by the intracellular application of cAMP and 3-isobutyl-1-methylxanthine. The results suggest that a GTP-binding protein is directly involved in the cAMP-independent receptor-mediated inhibition of voltage-dependent Ca2+ channels.
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PMID:A guanine nucleotide-binding protein mediates the inhibition of voltage-dependent calcium current by somatostatin in a pituitary cell line. 243 11

1. Intracellular recordings were made from neurones in the submucous plexus of the guinea-pig caecum and ileum. 2. Somatostatin hyperpolarized more than 90% of the neurones. The lowest effective concentration was 300 pM and the maximum hyperpolarization (about 30-35 mV) was caused by 30 nM. Under voltage clamp at -60 mV, somatostatin caused outward currents which reached a maximum of 350-700 pA. 3. The hyperpolarization or outward current reversed polarity at a membrane potential (about -90 mV in control solutions) which changed according to the logarithm of the external potassium concentration. 4. The somatostatin current showed inward rectification; when the inward rectification of the resting membrane was prevented by extracellular caesium or rubidium, the inward rectification of the somatostatin current also disappeared. 5. A potassium conductance with the same properties was increased by alpha 2-adrenoceptor agonists and by delta-opioid receptor agonists; however, the effects of somatostatin were unaffected by antagonists at alpha 2- or delta-receptors. The somatostatin analogue, cyclo-aminoheptanoyl-Phe-D-Trp-Lys-(benzyl)Thr, also did not antagonize the actions of somatostatin. 6. The hyperpolarization (or outward current) was unaffected by forskolin, cholera toxin, sodium fluoride, phorbol esters or intracellular application of adenosine 5'-O-(3-thiotriphosphate) (ATP-gamma-S). However, when the recording electrode contained guanosine 5'-O-(3-thiotriphosphate) (GTP-gamma-S) the hyperpolarizations reversed only partially when somatostatin application was discontinued, and repeated applications caused the membrane potential to approach and remain close to the potassium equilibrium potential. 7. It is concluded that somatostatin increases the conductance of a set of inwardly rectifying potassium channels in submucous plexus neurones. The coupling between somatostatin receptor and ion channel involves a guanosine 5'-triphosphate-binding protein, but is not likely to result from changes in intracellular levels of cyclic adenosine 3',5'-monophosphate.
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PMID:Somatostatin increases an inwardly rectifying potassium conductance in guinea-pig submucous plexus neurones. 245 Sep 94

The hypothalamic peptide somatostatin (SRIF) suppresses secretory activity in phenotypically distinct pituitary endocrine cells. We have used tight-seal whole-cell recording techniques to study the peptide's effects on the electrical properties of tumor pituitary cells derived from rat (GH3/B6) and human adenomas that secrete human PRL in a SRIF-sensitive manner. Both cell types exhibited qualitatively similar electrophysiological properties and electrical responses to SRIF. Under the experimental conditions employed the majority of cells spontaneously generated Ca2+-dependent actions potentials. The actions of the peptide on cellular excitability were markedly affected by the presence of horse and fetal calf sera. Without these additives the electrical responses faded and could not be studied in detail. Therefore, recordings were conducted in media containing sera. In the presence of sera almost all cells spontaneously generated Ca2+ action potentials, and peptide-induced changes in excitability were well preserved. SRIF depressed spontaneous and evoked action potential activity in a dose-dependent manner at concentrations that reduced intracellular free calcium ([Ca2+]i) and suppressed basal PRL release. Current and voltage clamp experiments revealed coordinate actions of the peptide on excitable membrane properties. SRIF (1 nM) enhanced a depolarization-activated, rapidly inactivating outward K+ current, thereby effectively reducing the rate at which action potentials occurred. Over the 10-1000 nM range SRIF slowly activated a virtually noninactivating K+ conductance over a wide range of membrane potential. This effectively hyperpolarized cells away from the threshold for triggering Ca2+-dependent action potentials and shunted the membrane. The peptide induced K+ conductance activated at the level of the resting potential was progressively lost during the intracellular dialysis of whole-cell recording. Dilute aqueous lysates of cells included in the patch pipette prevented much of the rundown of this SRIF-induced electrical response while inclusion of an ATP-regenerating system preserved some of the peptide action. Over the 10-100 nM concentration range SRIF also reduced voltage-dependent Ca2+ current. Furthermore, pretreatment of cells with pertussis toxin abolished SRIF action on cellular excitability, suggesting that SRIF can regulate the function of ionic channels through GTP-binding proteins (G proteins). The results demonstrate that SRIF acts coordinately on the primary conductances expressed in tumor PRL cells to attenuate or block Ca2+ action potential generation and thus Ga2+ entry from extracellular sources.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Somatostatin blocks Ca2+ action potential activity in prolactin-secreting pituitary tumor cells through coordinate actions on K+ and Ca2+ conductances. 245 3

Somatostatin (SS) inhibits secretion from many cells, including clonal GH3 pituitary cells, by a complex mechanism that involves a pertussis toxin (PTX)-sensitive step and is not limited to its cAMP lowering effect, since secretion induced by cAMP analogs and K+ depolarization are also inhibited. SS also causes membrane hyperpolarization which may lead to decreases in intracellular Ca2+ need for secretion. Using patch clamp techniques we now demonstrate: 1) that both (SS) and acetylcholine applied through the patch pipette to the extracellular face of a patch activate a 55-picosiemens K+ channel without using a soluble second messenger; 2) that, after patch excision, the active state of the ligand-stimulated channel is dependent on GTP in the bath, is abolished by treatment of the cytoplasmic face of the patch with activated PTX and NAD+, and after inactivation by PTX, is restored in a GTP-dependent manner by addition of a nonactivated human erythrocyte PTX-sensitive G protein, and 3) that the 55-picosiemens K+ channel can also be activated in a ligand-independent manner with guanosine [gamma-thio] triphosphate (GTP gamma S) or with Mg2+/GTP gamma S-activated erythrocyte G protein. We call this protein GK. It is an alpha-beta-gamma trimer of which we have previously shown that the alpha-subunit is the substrate for PTX and that it dissociates on activation with Mg2+/GTP gamma S into alpha-GTP gamma S plus beta-gamma. A similarly activated and dissociated preparation of GS, the stimulatory regulatory component of adenylyl cyclase, having a different alpha-subunit but the same beta-gamma-dimer, was unable to cause K+ opening.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Reconstitution of somatostatin and muscarinic receptor mediated stimulation of K+ channels by isolated GK protein in clonal rat anterior pituitary cell membranes. 245 51

1. Membrane properties and somatostatin effects were studied in cultured locus coeruleus neurones from neonatal rats by using the whole-cell version of the patch clamp technique. 2. The current-voltage relationship of the resting cell revealed an inward-going rectification. The inward currents developed almost instantaneously upon hyperpolarizing the membrane under voltage clamp, and at large negative potentials the inward current showed a time-dependent inactivation. Extracellularly applied Cs+ or Ba2+ (0.1 mM) inhibited the inward current in a voltage-dependent manner. 3. Application of somatostatin (0.01-1 microM) produced an increase in membrane conductance. Somatostatin-induced currents were calculated by subtracting the control current from the current during the somatostatin-induced response. The somatostatin-induced current developed almost instantaneously with hyperpolarization and did not show any time-dependent inactivation. The current-voltage relationship of the somatostatin-induced current exhibited a rectification in the inward direction and showed a reversal potential. The reversal potentials were close to the K+ equilibrium potential. 4. Extracellular Cs+ or Ba2+ (0.1 mM) inhibited the somatostatin-induced currents in a voltage-dependent manner, the effectiveness increasing with hyperpolarization. The somatostatin-induced hyperpolarization was not affected by apamin (20 nM) or by charybdotoxin (100 nM). 5. These results indicate that the somatostatin-induced conductance is very similar to the inward-rectification conductance. Because the somatostatin-induced inward rectification did not exhibit a time-dependent inactivation, this rectification and the inward rectification in the control neurones may arise from two different channels. 6. Pre-treatment of neurones with pertussis toxin abolished the somatostatin-induced response, but did not affect the resting inward rectification. When GTP gamma S was applied intracellularly, somatostatin produced an irreversible activation of the inward rectification conductance. The somatostatin-induced hyperpolarization may therefore be mediated through a pertussis toxin-sensitive GTP-binding protein.
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PMID:Somatostatin induces an inward rectification in rat locus coeruleus neurones through a pertussis toxin-sensitive mechanism. 247 50


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