Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.11.13 (protein kinase C)
 49,245 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The hypothalamus has the highest concentration of proglucagon-derived peptides (Pgdp's) in the brain, however, the control of the synthesis and secretion of these peptides is not understood. The goal of our studies was to examine in detail the regulation of synthesis and secretion of Pgdp's in the hypothalamus. Hypothalamic cultures were prepared from fetal rats on day 19-21 of gestation and Pgdp's in media and cells were determined by radioimmunoassay after treatment with test agents. Dibutyryl cyclic AMP or forskolin, activators of protein kinase A, markedly stimulated both Pgdp synthesis (by 5-fold) and secretion (by 10-fold) after 24 h of treatment (p < 0.05). The effects of protein kinase A stimulation on Pgdp's in the hypothalamus were greater than seen in our previous studies with the Pgdp-producing pancreatic A and intestinal L cells. Therefore there are tissue-specific differences with regard to the magnitude of the response of Pgdp's to protein kinase A stimulation. Consistent with an involvement of protein kinase A in hypothalamic Pgdp synthesis and secretion, somatostatin-14, an inhibitor of protein kinase A, was found to inhibit Pgdp synthesis and secretion in a dose-dependent fashion (p < 0.05). Phorbol myristate acetate (PMA), a stimulator of protein kinase C, did not significantly affect the synthesis or secretion of Pgdp's at 6 h, but significantly stimulated Pgdp secretion after 24 h (p < 0.05). The inactive phorbol ester, phorbol triacetate was without effect on Pgdp synthesis or secretion after 24 h of incubation (p > 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Control of proglucagon-derived peptide synthesis and secretion in fetal rat hypothalamus. 133 38

Somatostatin-14 (SRIF-14) inhibited, in a concentration-dependent manner, LH- and forskolin-stimulated cyclic adenosine monophosphate (cAMP) induction in porcine granulosa and luteal cells. The inhibitory effect of SRIF-14 on hormone-induced cAMP generation was more potent in porcine ovarian cells than in the GH-3 pituitary cell line. The inhibitory effect of SRIF-14 was impeded by neutralizing its biological activity with specific antiserum. Preincubation of luteal and granulosa cells with phorbol 12-myristate 13-acetate (PMA) enhanced LH- and forskolin-stimulated cAMP levels. SRIF-14 failed to inhibit LH- or forskolin-stimulated cAMP levels in cells preincubated with PMA. It is concluded that SRIF-14 inhibits hormone-stimulated cAMP induction in the porcine ovary. LH-induced protein kinase C activation may be physiologically important to alleviate the inhibitory effects of SRIF-14.
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PMID:Inhibitory action of somatostatin-14 on hormone-stimulated cyclic adenosine monophosphate induction in porcine granulosa and luteal cells. 135 68

Somatostatin (SRIF) reduces growth hormone releasing hormone (GRF)-stimulated growth hormone (GH) release from avian and mammalian adenohypophyseal cells. The present studies examined the intracellular mechanisms mediating SRIF inhibition of GRF-stimulated GH release from chicken pituitary cells. Increases (P less than 0.05) in GH release were observed in the presence of (1) GRF; (2) the adenylyl cyclase stimulator, forskolin; (3) a cAMP analog, 8-bromo-cAMP; (4) the phosphodiesterase inhibitor 3-isobutyl-l-methyl-xanthine (IBMX) combined with GRF; (5) a tumor-promoting phorbol ester and protein kinase C activator, phorbol 12-myristate, 13-acetate (PMA); (6) a diacylglycerol analog, 1,2-dioctanoyl-glycerol (DiC8); and (7) a calcium ionophore, A23187, alone and in combination with PMA. Somatostatin (10 ng/ml) reduced the release of GH stimulated by GRF, forskolin, and 8-bromo cAMP and the GRF-provoked release of GH in the presence of IBMX (P less than 0.05). Somatostatin, however, did not influence GH release in the presence of the protein kinase C activators, PMA or DiC8, or the calcium ionophore A23187. These data suggest that SRIF inhibits GRF-provoked GH release by reducing the ability of the cAMP-protein kinase A but not of the calcium or protein kinase C intracellular message pathways to stimulate GH release.
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PMID:Possible involvement of adenylyl cyclase-cAMP-protein kinase a pathway in somatostatin inhibition of growth hormone release from chicken pituitary cells. 170 26

The effects of endogenous hypothalamic neurohormones and activators of second messenger signalling systems on the secretion of GH and on cell content of GH mRNA of cultured bovine adenohypophysial cells were studied. Synthetic bovine GH-releasing factor (bGRF; 100 nmol/l) increased secretion of GH by bovine adenohypophysial cells five-fold relative to control. Forskolin (an adenyl cyclase activator; 10 mumol/l) and the synthetic cyclic AMP analogue dibutyryl cyclic AMP (dbcAMP; 1 mmol/l) increased secretion of GH by 1.9- and 1.7-fold respectively, relative to control. The protein kinase C activator phorbol 12-myristate 13-acetate (PMA), provided at 1 mumol/l or 10 nmol/l, increased GH secretion by 6.6- and four-fold respectively, relative to control. Somatostatin-14 (SRIF-14) attenuated basal, bGRF-, forskolin- and dbcAMP-stimulated secretion of GH by 40, 49, 47 and 67% respectively, but did not, however, diminish PMA-stimulated GH secretion. The content of GH mRNA in cultured bovine adenohypophysial cells increased 2.2-, 1.7- and 3.2-fold by administration of bGRF, forskolin and PMA respectively, relative to control. Although GH mRNA content was unchanged by SRIF-14 treatment relative to control, SRIF-14 did reduce bGRF-stimulated bGH mRNA content by 67%. This study demonstrates that mechanisms subserving GH secretion in bovine adenohypophysial cells (e.g. adenyl cyclase and protein kinase C) may be coupled with mechanisms which regulate expression of the GH gene or with factors affecting message stability.
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PMID:Modulation of growth hormone (GH) secretion and GH mRNA levels by GH-releasing factor, somatostatin and secretagogues in cultured bovine adenohypophysial cells. 197 Oct 2

A somatomammotropic cell line (P0) derived from adult rat pituitaries has been maintained in culture for 2 yr. Secretion of GH and PRL by this cell line has been studied in response to hypophysiotropic peptides known to affect the release of both hormones as well as agents that affect second messenger systems in an attempt to characterize the stimulus-secretion mechanisms used by these cells. GH and PRL release during short term (4 h) incubations of P0 cells and primary cultures of dispersed rat pituitary cells was initially measured in response to GRF, TRH, vasoactive intestinal peptide (VIP), and SRIF. In P0 cells, the minimal effective dose of each of the hypophysiotropic peptides was comparable with respect to GH and PRL secretion. The effects of TRH and VIP were similar to those in freshly dispersed cells with respect to PRL release, whereas those of GRF and SRIF were less potent with respect to GH release. The stimulation of GH and PRL release in P0 cells by adenylate cyclase-related agents ((Bu)2 cAMP and forskolin) was comparable to that for GH secretion in mature somatotrophs but much greater than that of PRL release in mature lactotrophs. Stimulation of GH and PRL release in P0 cells by protein kinase C-related agents (diacylglycerol and phorbol ester) was also similar to that observed for GH release from mature pituitary cells, whereas minimal or undetectable effects were observed on PRL release from mature cells. The results indicate that the P0 somatomammotropic cell line possesses receptors, second messenger systems, and secretory characteristics of both somatotrophs and lactotrophs, although where differences exist, there is more resemblance to somatotrophs. They also demonstrate that the responses to each of the agents studied are bihormonal and appear to be regulated by a common mechanism.
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PMID:Growth hormone and prolactin secretion in cultured somatomammotroph cells. 197 45

We have used isolated canine parietal cells to examine the receptor and postreceptor events mediating the inhibitory effects of somatostatin on acid secretion. Somatostatin-14 (S14) and somatostatin-28 (S28) dose dependently inhibited parietal cells stimulated by secretagogues that activate both the adenylate cyclase/cyclic adenosine monophosphate and the inositol phospholipid/protein kinase C cascades. The inhibitory action was mediated via a specific cell surface receptor that consists of a single subunit protein (molecular weight 99,000 d). This receptor recognized S14 and S28 equally well. Somatostatin inhibited parietal cell activity via mechanisms that are both dependent on and independent of a pertussis toxin-sensitive inhibitory guanine nucleotide binding protein.
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PMID:Cellular mechanisms of somatostatin action in the gut. 197 8

Digital imaging microscopy using the calcium-sensitive indicator probe fura-2 was combined with a reverse hemolytic plaque assay (RHPA) for growth hormone (GH) secretion. This technique allows dynamic measurements of the cytosolic free calcium concentration ([Ca2+]i) in individual pituitary somatotropes. Stimulation by growth hormone-releasing factor (GRF) increases, whereas somatostatin (SRIF) reduces [Ca2+]i in this cell type. [Ca2+]i increased in somatotropes when the cellular content of adenosine 3',5'-cyclic monophosphate (cAMP) was elevated by 1) activating cellular adenylate cyclase with forskolin (5 microM) and 2) treatment with the cAMP-analogues dibutyryl-cAMP (1 mM) or 8-bromo-cAMP (5 mM). The forskolin-induced calcium rise was abolished in the absence of extracellular calcium. This indicates that cAMP increases the influx of calcium into the cytosol and thereby stimulates hormone release. When forskolin was given in combination with SRIF (10 nM), [Ca2+]i decreased to the same level reached with SRIF treatment alone, indicating a site of action distal to the generation of cAMP. Activating protein kinase C with the phorbol ester 12,13-phorbol dibutyrate (PDB; 100 nM) increased [Ca2+]i as well. Again, this effect was dependent on extracellular calcium and blocked when PDB and SRIF were applied simultaneously. Combined stimulation with GRF plus PDB did not augment the response of [Ca2+]i over GRF treatment alone.
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PMID:Cytosolic free calcium in normal somatotropes: effects of forskolin and phorbol ester. 256 52

To examine the potential mechanisms by which somatostatin inhibits gastric acid secretion we studied its effects on isolated canine gastric parietal cells. Using 125I-[Leu8-D-Trp22-Tyr25]somatostatin-28 as ligand, we identified somatostatin-binding sites in parietal cell-enriched fractions of fundic mucosa. Two binding sites with respective dissociation constants of 3.2 X 10(-9) and 2.1 X 10(-7) M were identified. Somatostatin-14 and -28 were equally potent both in displacing bound ligand and in inhibiting parietal cell activity as measured by [14C]aminopyrine uptake. Pertussis toxin reversed the ability of somatostatin to inhibit the uptake of [14C]aminopyrine and production of cAMP by parietal cells stimulated with histamine and forskolin but not with dibutyryl cAMP or pentagastrin. Furthermore, somatostatin had no effect on parietal cell membrane inositol phospholipid turnover or changes in protein kinase C (Ca2+/phospholipid-dependent enzyme) activity induced by carbachol or pentagastrin. These data indicate that somatostatin directly inhibits parietal cell activity via mechanisms both dependent on and independent of the pertussis toxin-sensitive inhibitory guanine nucleotide-binding protein.
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PMID:Mechanisms for direct inhibition of canine gastric parietal cells by somatostatin. 288 65

The effect of phorbol diester tumour promoters on the release of growth hormone (GH) and prolactin (Prl) was studied in rat pituitary cells cultured in monolayer. 12-O-tetradecanoyl phorbol-13-acetate (TPA), the most potent phorbol ester, stimulated GH accumulation in the cultured medium in a dose-dependent manner. TPA also stimulated Prl accumulation. A time course study indicated that TPA mainly stimulates release of GH. The maximal stimulation of GH release by TPA (100 ng/ml) was 3-4-fold over control. Phorbol-12,13-dibutyrate (PDB), another tumour-promoting phorbol ester, stimulated GH release to an extent similar to that of TPA, while a biologically inactive compound, phorbol-12,13-diacetate (PDA), had no effect. TPA-stimulated GH release was not affected by the presence of indomethacin, an inhibitor of prostaglandin (PG) synthesis, indicating that PG is not involved in the process of TPA-stimulated GH release. Co++, a competitive antagonist of Ca++, at 2.0 mM completely suppressed the GH release induced by TPA, and this inhibition was partially reversed by the addition of 2.0 mM Ca++. Verapamil, a Ca++ channel blocker, reduced TPA-stimulated GH release, and trifluoperazine, an inhibitor of Ca-calmodulin formation, had a similar effect. Somatostatin (SRIF) also inhibited the GH release by TPA. These observations are compatible with the idea that Ca++ may be involved in the process of TPA-stimulated GH release. Since TPA has been reported to activate a Ca++- and phospholipid-dependent protein kinase (protein kinase C), it is possible that TPA stimulate GH release by activating the enzyme. Further studies are required to clarify this point.
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PMID:Effect of phorbol esters on the release of growth hormone and prolactin from rat pituitary cells cultured in monolayer. 614 63

GH secretory patterns undergo marked change during early mammalian development. The factors that underlie these changes and the major components of signal transduction in the immature somatotrophs are not fully understood. Increasing evidence suggests that protein kinase C (PKC) plays a central role in perinatal organ differentiation and function. To evaluate the possible role of PKC as a mediator of GH secretion from immature pituitaries, we tested the effects of the PKC activating phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA), alone or together with GH-releasing factor (GRF), somatostatin (SRIF), and Ca2+ modifying agents; an inactive phorbol analogue (4 alpha-12-13-didecanoate; 4 alpha-PDD), and phospholipase C on GH release from pituitary cell cultures from perinatal and mature rats. Pituitary primary cell cultures were prepared from fetal (day 20 of 21.5 days of gestation), 2-day-old, 12-day-old, and adult male (2- to 4-month-old) rats. Each experiment was performed on at least three separate occasions. The magnitude of TPA (0.15-150 nM)-induced GH release was markedly age-dependent, fractional GH release being greatest from pituitaries of fetal and newborn rats, and least from those of adults (P < 0.001). Further, the minimum dose of TPA required to stimulate GH release over basal levels was tenfold higher for adult pituitaries (15 nM) than for perinatal pituitaries (1.5 nM). Phospholipase C (1 and 10 U/ml) also caused greater fractional GH release from neonatal pituitaries than from adult pituitaries (P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Ontogeny of the GH response to phorbol ester and phospholipase C in rat pituitary cells. 761 64


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