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)

The cytosolic free calcium concentration and cumulative GH release were measured simultaneously in normal pituitary cells. This was made possible by a novel combination of fluorescence microscopy using the calcium indicator fura-2 and a reverse hemolytic plaque assay. GRF (10 nM) rapidly increased the intracellular free calcium concentration ([ Ca2+]i) from a basal level of 234 +/- 17 nM (mean +/- SE) to a peak value of 480 +/- 61 nM 1 min after stimulation. This GRF-induced calcium rise was totally abolished in calcium-free medium or in the presence of calcium channel blockers cobalt chloride (2 mM) and verapamil (100 microM). When somatostatin (SRIF; 1 nM) was added after basal recordings, cytosolic calcium decreased to 96 +/- 23 nM in identified somatotropes. [Ca2+]i returned to baseline upon the removal of SRIF inhibition. This rebound was higher when a sequential treatment of SRIF followed by GRF was applied. Exposing cells to a combination of GRF (10 nM) plus SRIF (1 nM) resulted in a decrease in [Ca2+]i identical to that caused by SRIF treatment alone. Despite the 10-fold excess of GRF, SRIF not only inhibited hormone secretion, but also totally overcame the GRF-induced rise of [Ca2+]i. In summary, stimulation by GRF increases cytosolic calcium in normal somatotropes. This increase is proposed to be due to the influx of calcium through membrane ion channels. In contrast, SRIF decreases [Ca2+]i. This might explain the cAMP-independent effects of this peptide. The effect of SRIF dominates over that of GRF with respect to both changes in [Ca2+]i and hormone release. Changes in the GH secretory rate are, therefore, accompanied by parallel changes in [Ca2+]i, both of which are primarily regulated by SRIF.
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PMID:Intracellular calcium concentration and growth hormone secretion in individual somatotropes: effects of growth hormone-releasing factor and somatostatin. 245 53

A novel combination of two single cell assays allowed the simultaneous measurement of intracellular calcium concentration and hormone secretion in normal pituitary cells. [Ca2+]i was recorded using the fluorescent Ca2+ indicator fura-2 and digital imaging microscopy. This technique was combined with a reverse hemolytic plaque assay for growth hormone in order to identify somatotropes and quantitate the amount of hormone released. A dynamic profile of rhythmic calcium oscillations was found in spontaneously secreting somatotropes. Each somatotrope displayed a distinct frequency (one pulse every 5-30 s) and amplitude (range 50-450 nM) generated asynchronously from cell to cell. The amount of growth hormone (GH) released correlated directly with both the frequency and amplitude of calcium oscillations at the level of single GH cells. Furthermore, calcium excursions in somatotropes were rapidly suppressed by either (i) removal of extracellular calcium, (ii) somatostatin (1 mM), or (iii) the calcium channel blockers cobalt (2 mM) and verapamil (100 microM). These observations demonstrate that spontaneous calcium oscillations are characteristic for normal somatotropes. These oscillations are related to spontaneous hormone secretion and due to influx through calcium channels in the membrane. Somatostatin, the physiologic inhibitor of GH secretion, suppresses calcium transients. These findings suggest that the intracellular signaling information may be encoded both in the frequency and amplitude of calcium oscillations.
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PMID:Spontaneous oscillations of intracellular calcium and growth hormone secretion. 245 18

The influence of membrane depolarization on somatostatin secretion and protein synthesis by fetal and neonatal cerebrocortical neurons was studied. Cortical cells obtained by mechanical dispersion were maintained as monolayer cultures for 8 days. The ability of fetal cerebrocortical and hypothalamic cells to release immunoreactive somatostatin (IR-SRIF) was confirmed. Total protein synthesis was determined by the incorporation of [3H]phenylalanine into trichloroacetic acid-precipitable proteins. To study the effect of acute depolarization on protein synthesis, cells were incubated for 30 min with [3H]phenylalanine or [3H]leucine and the depolarizing agent. In fetal cerebrocortical cells, potassium (30 and 56 mM) decreased protein synthesis and RNA levels and increased IR-SRIF release. Depolarization by veratridine, a sodium channel activator, induced a similar effect. The effect of veratridine on IR-SRIF and protein synthesis was reversed by tetrodotoxin, a sodium channel blocker, or verapamil, a calcium channel blocker. These findings suggest that protein synthesis by cerebrocortical cells is decreased in fetal brain cells by membrane depolarization and is dependent on Na+ and Ca2+ entry into cells. In postnatal (day 7) cerebrocortical cells, depolarization induced by high potassium concentrations led to a concomitant increase in protein synthesis, RNA content, and somatostatin release. These findings indicate that depolarization of the cellular membrane is coupled to an increase in protein synthesis in neonatal, but not in fetal, dispersed brain cells.
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PMID:Divergent effects of acute depolarization on somatostatin release and protein synthesis in cultured fetal and neonatal rat brain cells. 246 35

The pattern of TSH secretion in man in pulsatile in addition to the well known circadian variation. The mechanism triggering TSH pulses remains unclear to date. Infusions of somatostatin or dopamine rapidly lowering basal TSH levels without suppressing the pulsatile pattern suggest that an episodic disinhibition exerted by a physiological inhibitor is not a likely cause. On the same basis, thyroid hormones do not appear to be candidates, since they similarly inhibit basal TSH levels after a time lag of several hours but again do not suppress pulsatile release of the hormone. In contrast, bolus injections of dexamethasone completely abolish pulsatile release of TSH for several hours despite a normal sensitivity of the pituitary to exogenous TRH, suggesting a hypothalamic action of the drug. The hypothesis that pulsatile TSH release might be governed by a pulsatile mode of a hypothalamic stimulator is supported by the observation that an infusion of nifedipine, a calcium channel blocker, which in vitro selectively inhibits the TRH effect on TSH but not prolactin secretion, exerts a comparable effect when it is infused in vivo.
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PMID:Physiological regulation of thyrotropin. 249 28

1. Somatotroph cells were obtained from pituitaries of adult male rats by dissociation, separation and enrichment on a continuous gradient of bovine serum albumin at unit gravity. They were kept in culture for 7-15 days before electrophysiological experiments. 2. Immunofluorescent staining of the resulting gradient fractions (numbered F2 to F9) indicated that the majority of somatotrophs (75-85%) were located in the heavy fractions (F8 and F9). However, a small percentage (15-20%) of cells in these fractions were identified as lactotrophs. 3. Perifusion experiments indicated that on the one hand release of growth hormone from somatotroph-enriched fractions was stable at the level of 6 ng (2 min)-1 (10(6) cells)-1 and was markedly inhibited by somatostatin (1.9 ng (2 min)-1 (10(6) cells)-1) but not by dopamine. On the other hand, in the same cell preparations, basal prolactin release (1.6 ng (2 min)-1 (10(6) cells)-1) was significantly reduced by dopamine (0.08 ng (2 min)-1 (10(6) cells)-1) but remained unchanged by somatostatin treatment. 4. The inhibitory effect of somatostatin on growth hormone release was dose dependent. This effect was not abolished by tetraethylammonium (40 mM) or 4-aminopyridine (5 mM), but somatostatin decreased high-potassium-induced release. 5. In all the cells recorded (n = 187), 14% (n = 26) displayed a low resting potential (less than -30 mV) and poor membrane resistance (less than 50 M omega). The recording was unstable and resting potentials decreased regularly to 0 mV in less than 5 min. The other 86% of the cells displayed resting potentials varying from -45 to -65 mV and had a membrane resistance of more than 150 M omega. Only cells which displayed these membrane characteristics showed clear responses to somatostatin or dopamine, and were therefore chosen for experiments. 6. In all the cells selected for the experiments (n = 161), 78% (n = 126) showed either triggered or spontaneous action potentials. The action potentials remained insensitive to sodium-free bath solution, but were reversibly blocked by the calcium channel blockers cobalt (5 mM) or nickel (5 mM). 7. When the cells were at resting potential, somatostatin induced a hyperpolarizing response associated with a decrease of membrane resistance. During this response, spontaneous or triggered action potentials were inhibited. The hyperpolarizing response induced by somatostatin was dose-dependent.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Electrophysiological responses to somatostatin of rat hypophysial cells in somatotroph-enriched primary cultures. 257 Aug 71

Thymosin fraction 5 (TF5) is a partially purified extract of bovine thymus containing 40-60 peptides. In addition to its well documented immunopotentiating effects, TF5 reportedly modulates the secretion of some hypothalamic peptides and pituitary hormones. In this study, TF5 (10-100 micrograms/ml) stimulated PRL release from normal, MtTW15, and 7315a cells and GH release from normal and MtTW15 cells, but had no apparent effect on LH release. No changes in intracellular cAMP or cGMP levels could be correlated with these responses. Stimulation of PRL release from perifused normal anterior pituitary cells was rapid, sustained, and concentration related. Although it had no apparent effect on normal prelabeled anterior pituitary cells with respect to 45Ca2+ efflux, the calcium channel blocker D-600 inhibited TF5-mediated hormone release from these cells. Additive increases in TRH-stimulated PRL release and GRF-stimulated GH release by TF5 suggested independent mechanisms of action. Dopamine (500 nM) blocked TF5-stimulated PRL release, but somatostatin (10-100 nM) had no effect on TF5-stimulated PRL or GH release. TF5 failed to affect either basal or TRH-induced polyphosphoinositide hydrolysis. Perifused normal anterior pituitary cells prelabeled with [3H]arachidonate responded to TF5 treatment with a liberation of radioactive arachidonate and/or its metabolites. BW755c, an inhibitor of all known catabolic pathways of arachidonic acid, blocked the ability of TF5 to stimulate PRL and GH release. Reversed phase HPLC separation of TF5 into five fractions resulted in two fractions that exhibited hormone-releasing activity. These data suggest that TF5 stimulates pituitary hormone release through a mechanism different from that ascribed to TRH or GRF. The stimulus-secretion coupling mechanism involves neither polyphosphoinositide hydrolysis nor cAMP generation, but appears to be dependent on the generation of arachidonate metabolites.
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PMID:Thymosin fraction 5 stimulates prolactin and growth hormone release from anterior pituitary cells in vitro. 282 78

Although dopamine inhibits PRL release from the normal anterior pituitary lactotroph, a conclusive demonstration of the mechanisms involved in this response has been impeded by the presence of other cell types in the anterior pituitary. To circumvent this problem, we have isolated a clonal cell line, designated MMQ, from the 7315a rat pituitary tumor. The MMQ cell is an exemplary model for our use because it only secretes PRL. Our studies show that dopamine inhibits secretagogue-induced PRL release from these cells. In addition, dopamine decreases the intracellular cAMP concentration in MMQ cells that have been exposed to forskolin, cholera toxin, or vasoactive intestinal polypeptide, each a stimulator of cAMP generation. This inhibition is, in turn, reversed by the dopamine antagonist haloperidol and by pertussis toxin, an inactivator of the GTP-binding coupling protein. Dopamine also decreases the uptake and fractional efflux of 45Ca2+ by MMQ cells that have been exposed to the calcium channel activator maitotoxin. It seems, therefore, that dopamine decreases PRL release from MMQ cells at least in part by decreasing intracellular cAMP levels and calcium uptake. In additional experiments, we have found that MMQ cells are responsive to somatostatin, estrogen, progesterone, and acetylcholine, but not to TRH, angiotensin II, neurotensin, or bombesin. Furthermore, these cells possess a functional protein kinase-C system, as evidenced by the increase in PRL release and decrease in stimulated intracellular cAMP levels that occur in response to treatment with phorbol diesters. We suggest that the MMQ cell line will prove a useful model system for study of the biochemical effects of dopamine and other factors that modify PRL release.
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PMID:Characterization of the MMQ cell, a prolactin-secreting clonal cell line that is responsive to dopamine. 284 8

Rat anterior pituitary cells, loaded with the calcium indicator dye fura-2 after primary culture, were challenged with prolactin and growth hormone secretagogues and inhibitory hormones. To initially validate the technique, the calcium channel activator maitotoxin effectively increased intracellular free calcium [( Ca++]i). Various concentrations of the secretagogues thyrotropin releasing hormone or angiotensin II induced peak increases in [Ca++]i within 15 sec, followed by a lower and prolonged plateau phase. The inhibitory hormones dopamine and somatostatin maximally reduced [Ca++]i by 15-20 sec, followed by a spontaneous return to baseline over 5-10 min. The receptor antagonists saralacin and spiperone blocked the angiotensin II and dopamine effects, respectively. Thus, fura-2 appears to be an adequate probe for resolving second-to-second changes in [Ca++]i induced by hormone receptor activation in anterior pituitary cells.
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PMID:Intracellular free calcium in rat anterior pituitary cells monitored by fura-2. 288 9

The regulation of TSH release in man was investigated using cell cultures derived from human pituitaries obtained within 24 h of accidental death. TRH stimulated TSH release in a dose-dependent manner. The ED50 was 2.9 +/- 0.6 (+/- SEM) nmol/L, similar to that reported for rat pituitary cell cultures. The release of TSH was calcium dependent, since the calcium channel antagonist verapamil inhibited TRH-stimulated TSH release, and the calcium ionophore A23187 stimulated TSH release. 12-O-Tetradecanoyl-phorbol-13-acetate stimulated TSH secretion, while dibuytryl cAMP had no effect. Epinephrine and serotonin stimulated TSH release, and dopamine and somatostatin inhibited TRH-stimulated TSH release. These findings have directly demonstrated that the regulation of TSH secretion by hypothalamic neuropeptides and biogenic amines in the human pituitary is similar to that in the rat. The development of a tissue culture system to study thyrotrophs from postmortem human pituitaries provides the means for detailed studies of the regulation of TSH secretion in man.
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PMID:Neuroendocrine regulation of thyrotropin release in cultured human pituitary cells. 289 Jun 53

The neuropeptide somatostatin inhibits prolactin release from GH4C1 pituitary cells via two mechanisms, inhibition of stimulated adenylate cyclase activity and an undefined cAMP-independent process. Somatostatin also hyperpolarizes GH4C1 cells and reduces their intracellular free Ca2+ concentration ([Ca2+]i) in a cAMP-independent manner. To determine whether these ionic changes were involved in the cAMP-independent mechanism by which somatostatin inhibited secretion, changes in cAMP levels were prevented from having any biological consequences by performing experiments in the presence of a maximal concentration of a cAMP analog. Under these conditions, inhibition of prolactin release by somatostatin required a transmembrane concentration gradient for K+ but not one for either Na+ or Cl-. However, elimination of the outward K+ gradient did not prevent somatostatin inhibition of vasoactive intestinal peptide-stimulated hormone release. Therefore, somatostatin's cAMP-mediated mechanism does not require a K+ gradient, whereas its cAMP-independent inhibition of secretion appears to result from a change in K+ conductance. Consistent with this conclusion, membrane hyperpolarization with gramicidin (1 microgram/ml) mimicked somatostatin inhibition of prolactin release. In addition, the K+ channel blocker tetrabutylammonium prevented the effects of somatostatin on the membrane potential, the [Ca2+]i and hormone secretion. Nonetheless, a K+ gradient was not sufficient for somatostatin action. Even in the presence of a normal K+ gradient, somatostatin was only able to inhibit prolactin release when the extracellular Ca2+ concentration was at least twice the [Ca2+]i. Furthermore, the calcium channel blocker, nifedipine (10 microM), which prevents the action of somatostatin to reduce the [Ca2+]i, specifically blocked inhibition of prolactin release via somatostatin's cAMP-independent mechanisms. Therefore, a decrease in Ca2+ influx through voltage-dependent Ca2+ channels produces both the fall in [Ca2+]i and inhibition of hormone secretion in response to somatostatin.
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PMID:Characterization of the cyclic AMP-independent actions of somatostatin in GH cells. II. An increase in potassium conductance initiates somatostatin-induced inhibition of prolactin secretion. 289 96


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