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)

Many different types of cells exhibit a supersensitivity of adenylate cyclase after chronic treatment with inhibitory drugs; this phenomenon is manifested by enhanced cAMP accumulation upon removal of the inhibitory drug. Acute treatment of wild-type S49 cells with the somatostatin analog SMS 201-995 (SMS) results in inhibition of cAMP accumulation. We have found that chronic SMS treatment of S49 cells results in enhanced isoproterenol- and forskolin-stimulated cAMP accumulation after removal of the SMS. The forskolin-stimulated cAMP synthetic rate was about 57% higher in SMS-pretreated cells (14.22 +/- 1.02 pmol of cAMP/10(6) cells/min) than in untreated control cells (9.08 +/- 0.84 pmol of cAMP/10(6) cells/min). The time course of forskolin-stimulated intracellular cAMP accumulation is complex, with desensitization of cAMP synthesis and marked egress of cAMP from the cells. We have modeled the forskolin-stimulated cAMP time course to a simple function incorporating the initial synthetic rate and rate constants for desensitization and elimination (degradation plus egress). The mathematical modeling suggests that the difference in forskolin-stimulated cAMP time courses between control and SMS-pretreated cells can be explained on the basis of a difference in initial synthetic rates. We tested the hypothesis that the SMS-induced change in forskolin-stimulated cAMP accumulation is triggered by the decrement in the concentration of intracellular cAMP caused by SMS. We studied two independently isolated mutants of S49 cells that are devoid of cAMP-dependent protein kinase activity (kin-). Although SMS acutely inhibits cAMP accumulation in both kin- mutants, neither mutant exhibited an enhanced forskolin-stimulated cAMP synthetic rate after chronic SMS treatment. These results suggest that cAMP-dependent protein kinase is important in the induction of adenylate cyclase supersensitivity in wild-type S49 cells. The mechanistic signal for induction of supersensitivity may be the decreased cAMP accumulation that occurs in response to stimulation of inhibitory receptors, although other hypothetical mechanisms may be invoked.
Mol Pharmacol 1989 Jan
PMID:Chronic somatostatin treatment induces enhanced forskolin-stimulated cAMP accumulation in wild-type S49 mouse lymphoma cells but not in protein kinase-deficient mutants. 256 3

Regulation of preprosomatostatin mRNA and tyrosine hydroxylase mRNA were examined in sympathetic neurons of the rat superior cervical ganglion (SCG). Surgical denervation of the adult SCG increased ganglion levels of preprosomatostatin (SS) mRNA more than 11-fold, and levels of the mRNA remained elevated 14 days after surgery. By contrast, denervation decreased levels of tyrosine hydroxylase (TH) mRNA. Potassium- or veratridine-induced membrane depolarization of cultured neonatal sympathetic neurons decreased levels of SS mRNA but elevated levels of TH mRNA. Sodium channel blockade with tetrodotoxin prevented the effects of veratridine on SS and TH mRNAs. In toto these observations suggest that transsynaptic nerve impulse activity and sympathetic neuron membrane depolarization decrease SS synthesis but increase TH synthesis at the mRNA level. Thus nerve impulse activity may alter the relative levels of different transmitters co-expressed in the same neuronal population by inhibiting levels of some species of mRNA while simultaneously stimulating levels of others.
Brain Res Mol Brain Res 1989 Jan
PMID:Differences in the effects of membrane depolarization on levels of preprosomatostatin mRNA and tyrosine hydroxylase mRNA in rat sympathetic neurons in vivo and in culture. 256 23

The regenerative and functional capacity of B-cells in the remaining pancreatic tissue after surgical removal of 40%, 60% and 80% of the pancreas was examined in 7 month old pigs (three animals in each group). Prior to resection and 1, 3 and 6 weeks after surgery, basal and glucose-stimulated levels of insulin and blood glucose were determined and compared with the preoperative data and that of sham-operated controls. For quantitative morphology, the volume of the resected specimen and the residual pancreatic tissue, 6 weeks after surgery, was determined and sections evaluated by immunocytochemistry (insulin, glucagon, somatostatin, pancreatic polypeptide) combined with morphometry. In the remaining pancreas, the volume density of the B-cells was increased by 19% (1.57-1.92 after 60% resection; p less than 0.02) and 56% (1.57-2.38 after 80% resection; p less than 0.02) 6 weeks after surgery, compared with the respective resected portion of the pancreas and the controls (n = 12). The non-B-cells gained between 0-10% (PP-cells), 10-20% (D-cells) and 30-40% (A-cells) in the different resection groups. As the number of B-cells per given islet area remained unchanged (mean 4.12 cells/0.25 mm2), the increased volume density was due to an increase in cell number rather than cell size. Insulin secretion (integrated values, 0-120 min), was not significantly impaired after 40% and 60% resection (2711 +/- 250 all preoperative samples; 3215 +/- 474 40% at 6 week intravenous glucose tolerance test (IV-GTT); 1677 +/- 109 60% at 6 week IV-GTT), although the glucose levels (integrated values) were increased during the IV-GTT. The 80% resected animals showed a significant decrease in the insulin response only 1 week after surgery (integrated values: 2711 +/- 250 all preoperative samples, compared with 1250 +/- 508 1 week IV-GTT; p less than 0.05), while the integrated glucose values during IV-GTT (0-120 min) were significantly elevated throughout the observation period. These results suggest a B-cell hyperplasia in the residual pancreas after resection, which may cope with a normal functional demand, but disclose functional abnormalities when challenged with an increased glucose load.
Virchows Arch B Cell Pathol Incl Mol Pathol 1989
PMID:Increase in B-cells in the pancreatic remnant after partial pancreatectomy in pigs. An immunocytochemical and functional study. 256 23

Quantitative in situ hybridization was used to examine the regional distribution of preprosomatostatin messenger RNA (PPSOM mRNA) in the dorsal striatum (caudo-putamen) of the mouse. In addition, because mesencephalic dopaminergic neurons project to the striatum where they play a role in the regulation of peptide-containing neurons, the effect of dopamine receptor blockade on the levels of striatal PPSOM mRNA was determined. Sagittal brain sections from male Swiss Webster mice were processed for in situ hybridization histochemistry using an 35S-radiolabelled RNA probe in order to quantify levels of PPSOM mRNA in individual neurons of the dorsal caudo-putamen using light microscopy and computer-assisted grain analysis. In control animals, individual neurons of the dorsolateral caudo-putamen had higher levels of PPSOM mRNA than did those of the medial part of the structure. Treated mice were injected with fluphenazine-N-mustard (FNM), an antagonist which, at the dose used (4 mumol/kg), irreversibly blocks dopamine D2 but not D1 receptors in the mouse striatum. FNM treatment (for 2 days, twice a day) produced an increase in striatal dopamine turnover and a decrease in PPSOM mRNA levels in the lateral, but not the medial striatum. The results indicate that there is a lateral to medial gradient in the levels of PPSOM mRNA per individual neuron in the dorsal caudo-putamen of control animals, which is abolished by FNM treatment. This suggests that intrinsic striatal somatostatinergic neurons are differentially regulated by dopamine, depending on their lateromedial location within the striatum.
Brain Res Mol Brain Res 1989 Mar
PMID:Regional distribution and regulation of preprosomatostatin messenger RNA in the striatum, as revealed by in situ hybridization histochemistry. 256 4

The levels of preprosomatostatin (preproSS) mRNA, somatostatin-like immunoactivity (SS-LI) (also known as somatotropin-release inhibitory factor, or SRIF), glutamic acid decarboxylase (GAD) activity and GAD mRNA were determined in several brain regions of amygdaloid-kindled rats. SS mRNA and SS increased in the cortex and striatum, while only SS increased in the hippocampus. No changes were detected in either GAD activity or GAD mRNA in any brain region. The data suggest that somatostatin may be one of the factors involved in the chain of events leading to kindled seizures.
Brain Res Mol Brain Res 1989 May
PMID:Amygdaloid kindling of rats increases preprosomatostatin mRNA and somatostatin without affecting glutamic acid decarboxylase (GAD) mRNA or GAD. 256 84

Treatment of the somatostatin (SRIF)-producing TT cell line with 1,25 dihydroxyvitamin D3 (1,25 D3) lowered intracellular SRIF mRNA and peptide concentration. In separate experiments, the cAMP analog 8-(4-chlorophenylthio)-cAMP stimulated a rapid increase in SRIF mRNA content of the TT cells and SRIF peptide secretion. To determine whether 1,25 D3 could inhibit either the transcriptional or secretory effects of cAMP, TT cells were pretreated with 1,25 D3 for 4 days followed by treatment with the cAMP analog. Pretreatment with 1,25 D3 inhibited the cAMP-mediated increase of SRIF mRNA, but had no effect on the secretory response. We conclude that the ability of 1,25 D3 to silence SRIF gene expression is more potent than cAMP enhancer activity but that 1,25 D3 has no effect on that portion of the cAMP-dependent pathway which regulates peptide secretion.
Mol Endocrinol 1989 Mar
PMID:1,25-Dihydroxyvitamin D3 silences 3',5'-cyclic adenosine monophosphate enhancement of somatostatin gene transcription in human thyroid C cells. 256 85

Free cytosolic calcium concentration, [Ca2+]i, in single rat pituitary cells can be measured with the fluorescent, calcium-sensitive probe fura-2 and digital image analysis. A reverse hemolytic plaque assay (RHPA) identifies somatotropes in the mixed population of pituitary cells. Previous studies showed that growth hormone releasing factor (GRF) stimulates growth hormone (GH) release from pituitary somatotropes by increasing the influx of calcium into the cell. Somatostatin reduced [Ca2+]i and inhibits hormone release presumably by closing calcium channels in the membrane. The calcium-ionophore bromo-A23187 rapidly increased [Ca2+]i from a baseline of 226 +/- 38 nM to a peak of 842 +/- 169 nM (mean +/- SEM) which was reached 30 s after exposure to the drug. This spike was followed by a sustained phase of elevated [Ca2+]i approximately 370 nM. When somatostatin (SRIF) (10 nM) was combined with ionophore treatment, the initial rise was preserved. However, the second phase was abolished and SRIF lowered [Ca2+]i to 57 +/- 7 nM. Depolarizing the cellular membrane with high extracellular potassium (60 mM) increased cytosolic calcium as well (797 +/- 178 nM); however, this was not affected by the addition of SRIF (988 +/- 71 nM). KCl depolarization in calcium-free medium (+1.5 mM EGTA) provoked no rise in cytosolic calcium. In contrast, after ionophore, the initial spike was preserved while the sustained phase of elevated [Ca2+]i was abolished. We conclude from these data that (1) membrane depolarization and ionophore treatment lead to an influx of calcium into the cytosol of normal pituitary somatotropes. (2) SRIF inhibits calcium influx induced by ionophore but not influx after depolarization with high potassium concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)
Mol Cell Endocrinol 1989 Jun
PMID:Ionophore bromo-A23187 reveals cellular calcium stores in single pituitary somatotropes. 256 28

We have measured the distribution of growth hormone (GH) mRNA or intron I sequences by in situ hybridization on ultrathin frozen sections of pituitaries removed from rats injected with saline, GH-releasing factor (GRF) or somatostatin. A 4-fold increase in labeling of the anterior lobe was observed after GRF, no changes with somatostatin. After ultrastructural in situ hybridization, labeling with the GH cDNA probe was specific to somatotrophs. Two populations of cells containing few or many secretory granules were labeled mainly in the cytoplasm or in both cytoplasm and nucleus. Some cells showed labeling at the perinuclear membrane. Hybridization with the GH intron I probe showed the same cell specificity with silver grains mainly located in the nucleus. After GRF, sequences hybridizing to growth hormone cDNA were increased mainly in the nucleus of somatotrophs when compared to mock-injected rats, indirectly suggesting an increase in the transcriptional activity of the growth hormone gene. After somatostatin, the density of labeling in the nucleus was increased suggesting that somatostatin may prevent the export of growth hormone mRNA molecules from the nucleus to the cytoplasm.
Mol Cell Endocrinol 1989 Aug
PMID:Ultrastructural distribution of growth hormone (GH) mRNA and GH intron I sequences in rat pituitary gland: effects of GH releasing factor and somatostatin. 257 Jul 21

We investigated the effect of somatostatin (SS) in guinea-pig ventricular muscles using a force transducer and a conventional microelectrode method. Instead of a negative inotropic effect in atrial muscles, SS (10(-11) to 10(-7) M) elicited a positive inotropic effect in ventricular muscles in a concentration-dependent fashion, without changing the time course of contraction. The positive inotropic effect of SS was accompanied by a significant enhancement of the slow action potentials and was suppressed by diltiazem and phentolamine. An increase of extracellular Ca2+ concentration or stimulation frequency enhanced the positive inotropic effect of SS. The positive inotropic effect of SS was not suppressed in the presence of propranolol, metoclopramide, cimetidine or indomethacin, and it appeared even under cold conditions. These results suggest that SS has a positive inotropic effect in guinea-pig ventricular muscle, which is at least partly due to an increase in the slow inward Ca2+ current.
J Mol Cell Cardiol 1989 Jun
PMID:Positive inotropic effect of somatostatin in guinea-pig ventricular muscles. 257 Aug 76

Relaxin is a hormone associated with pregnancy that relaxes uterine smooth muscle and softens the connective tissues of the cervix and pelvis. In spite of these well-characterized tissue responses, the second messenger system linked to the relaxin receptor and the range of target tissues are only modestly understood. We found that relaxin enhanced the cyclic AMP levels in anterior pituitary cells from adult female rats. Relaxin induced a maximal 5.7 +/- 0.5-fold (mean +/- S.E.M.) stimulation of cyclic AMP accumulation and had an excitatory concentration for half-maximal effect (EC50) of 0.4 +/- 0.1 nM, while human relaxin A and B chains had no such activity (EC50 greater than 1 microM). Pertussis toxin amplified the efficacy of relaxin by 1.5 +/- 0.1-fold, indicating the intervention of a G coupling protein. The response to relaxin was reversible with washing, and desensitized slowly with continuous exposure to relaxin. In an attempt to define the physiological role for relaxin at the anterior pituitary, we found that two of the major hypophysiotrophic hormones of the brain (dopamine and somatostatin) markedly inhibited the relaxin stimulation of cyclic AMP. There was also a significant correlation of the response magnitude with the gender of the donor rat. Anterior pituitary cells from adult males exhibited a mean twofold maximal stimulation after relaxin, compared with the sixfold increase measured in cells from female rats. We hypothesize a novel physiological function of relaxin, that of signalling the feminine anterior pituitary.
J Mol Endocrinol 1989 Nov
PMID:Characterization of relaxin-stimulated cyclic AMP in cultured rat anterior pituitary cells: influence of dopamine, somatostatin and gender. 257 41


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