Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: UMLS:C0043167 (pertussis)
19,595 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A role for cAMP in the process of LHRH release was suggested several years ago, but only recently has the validity of this notion come under close scrutiny. In the present experiments we have used three probes, which stimulate adenylate cyclase activity via different mechanisms, to determine whether an increase in endogenous cAMP results in LHRH release from the hypothalamus of prepubertal female rats. Median eminences from juvenile, 28-day-old animals were incubated in vitro with either forskolin (F), cholera toxin (CT), or pertussis toxin (PT). All three substances enhanced LHRH release. The estimated ED50 values were 28.7 microM and 20.0 ng/ml, for F and PT, respectively. The effect of CT appeared biphasic and thus no ED50 could be calculated. None of these agents increased the release of prostaglandin E2 (PGE2), an obligatory component in the process of norepinephrine-induced LHRH secretion. Doses of PGE2 and F, which were maximally effective in stimulating LHRH release when administered separately, did not produce any further response when administered concomitantly, thus suggesting that PGE2 and F act along a common pathway. Blockade of phosphodiesterase activity with 1-methyl-3-isobutylxanthine increased LHRH secretion without enhancing PGE2 release, implying that cAMP metabolism was elevated in the median eminence nerve terminals in vitro. Addition of 1-methyl-3-isobutylxanthine augmented the LHRH response to CT and PT, but it did not increase further the already marked LHRH response to PGE2 or F. The results indicate that both an increase in adenylate cyclase activity and a decrease in phosphodiesterase activity lead to LHRH release from the median eminence. They also suggest that, upon proper (neurotransmitter?) stimulation, cAMP production increases subsequent to the activation in PGE2 synthesis, which itself causes LHRH release. Furthermore, the capacity of PT to induce LHRH release suggests the involvement of an inhibitory guanine nucleotide-binding regulatory protein in transducing inhibitory inputs impinging on LHRH-secreting neurons.
...
PMID:Stimulation of cyclic adenosine 3',5'-monophosphate production enhances hypothalamic luteinizing hormone-releasing hormone release without increasing prostaglandin E2 synthesis: studies in prepubertal female rats. 241 Feb 36

Voltage-dependent Ca2+ currents appear to be involved in the actions of hormones that regulate pituitary secretion. In order to investigate modulation of Ca2+ currents by release-inducing and release-inhibiting hormones, we performed whole-cell clamp experiments in the pituitary cell line GH3. The resting potential was approximately -40 mV; spontaneous action potentials were observed in the majority of cells. Superfusion of cells with the stimulatory hormone, LHRH, depolarized the plasma membrane to approximately -10 mV, whereas the inhibitory hormone, somatostatin, caused hyperpolarization to approximately -60 mV; both hormones suppressed spontaneous action potentials. Under voltage clamp conditions, GH3 cells exhibited slowly and fast inactivating Ca2+ currents. LHRH increased whereas somatostatin decreased the slowly inactivating currents; fast inactivating currents were not affected by these hormones. The stimulatory effect of LHRH was not mimicked by intracellularly applied cAMP. In contrast to vasoactive intestinal peptide and forskolin, LHRH did not activate adenylate cyclase in membranes of GH3 cells, but rather appeared to cause inhibition of the enzyme. Hormonal stimulation and inhibition of inward currents were abolished by pretreatment of the cells with pertussis toxin. In membranes of GH3 cells, we identified a pertussis toxin-sensitive G-protein of the Gi-type and Go. We conclude that LHRH and somatostatin modulate voltage-dependent Ca2+ currents via cAMP-independent mechanisms involving pertussis toxin-sensitive G-proteins. The occurrence of both pertussis toxin-sensitive hormonal stimulation and inhibition of voltage-dependent Ca2+ currents in one cell type suggest that these opposite regulations are mediated by distinct G-proteins.
...
PMID:Cyclic AMP-independent, dual regulation of voltage-dependent Ca2+ currents by LHRH and somatostatin in a pituitary cell line. 245 19

Addition of gonadotropin releasing hormone (GnRH) to pituitary cells prelabeled with [32P]Pi or with myo-[2-3H]inositol, resulted in a rapid decrease in the level of [32P]phosphatidylinositol 4,5-bisphosphate (approximately 10 s), and in [32P]phosphatidylinositol 4-phosphate (approximately 1 min), followed by increased labeling of [32P]phosphatidylinositol and [32P]phosphatidic acid (1 min). GnRH stimulated the appearance of [3H]myo-inositol 1,4,5-trisphosphate (10 s), [3H]myo-inositol 1,4-bisphosphate (15 s), and [3H]myo-inositol 1-phosphate (1 min) in the presence of Li+ (10 mM). Li+ alone stimulated the accumulation of [3H]myo-inositol 1-phosphate and [3H]myo-inositol 1,4-bisphosphate but not [3H]myo-inositol 1,4,5-trisphosphate, but had no effect on luteinizing hormone release. The effect of GnRH on inositol phosphates (Ins-P) production was dose-related (ED50 = 1-5 nM), and was blocked by a potent antagonist [D-pGlu,pClPhe,D-Trp]GnRH. Elevation of cytosolic free Ca2+ levels ([Ca2+]i), by ionomycin and A23187 from intracellular or extracellular Ca2+ pools, respectively, had no significant effect on [3H]Ins-P production. GnRH-induced [3H]Ins-P production was not dependent on extracellular Ca2+ and was noticed also after extracellular or intracellular Ca2+ mobilization by A23187 or ionomycin, respectively. The effect of GnRH on [3H]Ins-P accumulation was not affected by prior treatment of the cells with the tumor promoter phorbol ester 12-O-tetradecanoylphorbol-13-acetate or with islet-activating protein pertussis toxin. These results indicate that GnRH stimulates a rapid phosphodiester hydrolysis of polyphosphoinositides. The stimulatory effect is not mediated via an islet-activating protein-substrate, is not dependent on elevation of [Ca2+]i, neither is it negatively regulated by 12-O-tetradecanoylphorbol-13-acetate which activates Ca2+/phospholipid-dependent protein C kinase. The results are consistent with the hypothesis that GnRH-induced phosphoinositide turnover is responsible for Ca2+ mobilization followed by gonadotropin release.
...
PMID:Gonadotropin-releasing hormone activates a rapid Ca2+-independent phosphodiester hydrolysis of polyphosphoinositides in pituitary gonadotrophs. 301 78

The control of M-current by muscarinic ACh receptors and luteinizing hormone releasing hormone (LHRH) receptors was studied in dialyzed frog sympathetic ganglion neurons. M-current was recorded in dialyzed cells without run-down or changes in its biophysical properties and could be reversibly suppressed by muscarine and teleost LHRH (t-LHRH). However, dialysis with internal solutions lacking ATP or substituting with APP(NH)P caused the loss of M-current, suggesting that dephosphorylation suppresses the activity of M-channels. M-current over-recovers after agonist addition and removal to a size 30% larger than control, as if latent channels are activated during the recovery. Dialysis of cells with the G-protein activators GTP gamma S, fluoride, and aluminum fluoride causes loss of M-current. G-protein activation by receptors was confirmed by dialysis with low concentrations of GTP gamma S in competition with GTP. This prevents the rapid loss of M-current, but addition of muscarine or t-LHRH caused irreversible loss of M-current, suggesting that both transmitter receptors do suppress M-current by activating a G-protein. Suppression of M-current was not affected by treatment with 0.1 microgram/ml pertussis toxin (IAP) for 24-48 hr. In addition, based on the lack of IAP-specific labeling of frog sympathetic neuron membrane proteins, no IAP-sensitive G-proteins are present in these cells. These results indicate that an IAP-insensitive G-protein couples muscarinic and LHRH receptors to the suppression of M-current.
...
PMID:Muscarine and t-LHRH suppress M-current by activating an IAP-insensitive G-protein. 313 47

The issue of whether the adenosine 3',5'-monophosphate (cAMP)-generating system contributes to luteinizing hormone (LH) release was addressed by using several complementary probes in vitro. Pertussis toxin is considered to modify covalently an inhibitory adenylate cyclase regulatory protein. Treatment of gonadotrophs with this toxin increased both basal LH release and the efficacy of gonadotropin-releasing hormone (GnRH)-stimulated LH release with no apparent effect on GnRH potency. Cholera toxin, which probably activates adenylate cyclase by covalently altering another regulatory protein, forskolin, which directly stimulates the catalytic subunit of adenylate cyclase, and the cAMP analogue 8-Br-cAMP amplified both basal LH release (in a dose-dependent manner) and GnRH-stimulated LH release after a lag of 1 (cholera toxin and 8-Br-cAmP) and 4 (forskolin) h. It is noteworthy that these belated effects occurred in spite of the fact that cellular cAMP accumulation was markedly increased within 30 min after cholera toxin and at 1 min after forskolin addition. There was no change in total radioimmunoassayable LH (cellular + released) in either the basal or GnRH-treated cells after cholera toxin and forskolin for up to 24 h. Finally, the forskolin-amplified LH release was reversible and calcium dependent because D-600, EDTA, and calcium-free medium inhibited this effect. These results, generated with three complementary probes that affect integral proteins of the adenylate cyclase complex, suggest a function for cAMP in modulating LH release.
...
PMID:LH release is facilitated by agents that alter cyclic AMP-generating system. 632 Jun 61

The LHRH receptor in alpha T3-1 gonadotrope cells was shown to bring about a marked and sustained activation of MAP kinase. This response was prevented by protein kinase C inhibition or down-regulation and could be partially mimicked by phorbol ester. Additional evidence for inhibition of this response by pertussis toxin and partial mimicry by mastoparan (in a pertussis toxin-sensitive manner) provides the first evidence for Gi/Go-mediated signal transduction by the LHRH receptor. This dual mechanism of MAP kinase activation appears to be exceptional amongst the G protein-linked receptors that have been investigated.
...
PMID:Activation of MAP kinase by the LHRH receptor through a dual mechanism involving protein kinase C and a pertussis toxin-sensitive G protein. 748 30

The effects of neuropeptide Y (NPY) on LHRH release from an immortalized cell line were investigated using a flow-through cell culture superfusion system. Immortalized hypothalamic GT1-7 cells were cultured for 72 h and superfused for a total of 180 min. In initial experiments, discrete 5-min pulses of NPY (10(-12)-10(-5) M) were administered to the cells. A clear dose-dependent stimulatory effect on NPY on LHRH release from the cells was observed with a calculated 50% effectiveness concentration of 33 nM. The stimulatory effects of brief NPY exposure were rapid and robust, e.g. reaching and maintaining levels of 173% over baseline for 20 min at the 10(-7) dose. The lowest dose of NPY that showed a significant effect was 10(-10) M; maximal responses were observed at 10(-6) M and reached a plateau thereafter. Control pulses of Dulbecco's modified Eagle's medium (DMEM) and 10(-6) M substance P or arg-vasopressin were also presented to the cells to serve as controls for our pulse protocol, and these challenges produced no significant LHRH responses. The NPY receptor antagonists, PYX1 and PYX2, at 10(-8) M, completely blocked the observed NPY responses in these cells. To assess the NPY receptor subtypes that mediate the NPY effects pharmacologically, GT1-7 cells were challenged with a Y1 receptor agonist, (Leu31Pro34)NPY, a Y2 receptor agonist, NPY(13-36), or peptide YY, at doses 10(-12)-10(-5) M. All four peptides stimulated LHRH release from GT1-7 cells with a rank-ordered potency of NPY = peptide YY > Y1 agonist = Y2 agonist. To examine possible signal transduction mechanism(s) involved in mediating this effect, pertussis toxin, RpcAMPs (cyclic adenosine-3'5'-monophosphothioate Rp diastereomer), Ca(2+)-free DMEM and TMB-8 (3, 4, 5-trimethoxybenzoic acid 8-(diethylamino) octylester) were used to treat the cells before and during superfusion with NPY. Treatment with pertussis toxin, RpcAMPs, and Ca(2+)-free DMEM did not significantly alter NPY-stimulated LHRH release responses to 10(-7) M NPY. However, the addition of 100 microM and 250 microM TMB-8 to Ca(2+)-free DMEM almost completely blocked this NPY effect, as did 10 microM ryanodine. Finally, the locus of action for this NPY effect was examined using tetrodotoxin to reduce action potential propagation in the GT1-7 cells. Tetrodotoxin treatment blocked the LHRH response to NPY by more than 50%.(ABSTRACT TRUNCATED AT 400 WORDS)
...
PMID:Neuropeptide Y stimulates luteinizing hormone-releasing hormone release from superfused hypothalamic GT1-7 cells. 792 25

Incubation of dispersed adenohypophyseal cells from intact male rats with Neuropeptide Y (NPY) or Peptide YY (YY) at 21 degrees C increased maximal 125I LHRHa binding (Bmax) by about 50%. In presence of 10(-7) M NPY, Bmax calculated from saturation isotherm curves was 15.3 +/- 1.9 fmoles x mg-1 proteins, as compared to 10 +/- 1 fmoles x mg-1 in control incubates. The increase was dose dependent with an EC50 of 6.3 +/- 1.8 10(-10) M NPY. Preincubation of the cells with pertussis toxin (PT, 15 ng/ml) for 24 h abolished the effect, suggesting coupling of NPY receptors to G alpha o or G alpha i proteins. NPY 10(-7) M inhibited basal and Forskolin 10(-5) M stimulated intracellular cyclic AMP formation by 31.9 +/- 3.4% and 30.6 +/- 2.3% respectively. Desensitization of protein kinase C by overnight preincubation of the cells with 10(-6) M phorbol ester (PMA) did not interfere with the effect of NPY. In contrast, W7, a calmodulin inhibitor, as well as H7, a protein kinase C inhibitor with a relatively wide spectrum, suppressed the effect of NPY with IC50 of 1.4 +/- 0.6 10(-6) M and 2.2 +/- 0.5 10(-5) M, respectively. Taken together, these results suggest that NPY is able to control unmasking of a cryptic LHRH receptor pool in pituitary cells by a process dependent upon both GTP binding proteins and calmodulin dependent protein kinase.
...
PMID:Neuropeptide Y enhances LHRH binding to rat gonadotrophs in primary culture. 817 May 23

The effect of thyrotropin-releasing hormone (TRH) and gonadotropin-releasing hormone-associated peptide (GAP) was studied on both secretion and intracellular free Ca2+ concentrations ([Ca2+]i) in human pituitary cells cultured from prolactin (PRL)-secreting tumors. Secretion was measured during a 30-min incubation period and we used a microspectrofluorimetric method in individual cells and indo-1 as the fluorescent probe. TRH (10(-8) M) significantly increased PRL release in five out of the six cell populations. In these five cases, more than 68% of individual cells responded to TRH by an increase in [Ca2+]i. No significant increase in PRL secretion was found in another culture in which TRH increased [Ca2+]i in only 37% of the cells. The effect of GAP (10(-7) M) was studied in five cell populations. In three of them, a decrease of 20% to 51% of the PRL basal secretory rate was observed under GAP. GAP inhibited [Ca2+]i in respectively 59%, 46% and 94% of the cells from these cultures. The inhibitory effect of GAP was blocked by a pertussis toxin (PT) pretreatment which demonstrates the involvement of a PT-sensitive G-protein in GAP action. In two other cultures, GAP did not significantly alter PRL secretion or individual cell [Ca2+]i. These observations suggest that GAP might play a role in the control of PRL secretion in the human.
...
PMID:Thyrotropin-releasing hormone and gonadotropin-releasing hormone-associated peptide modulation of [Ca2+]i in human lactotrophs. 824 9

Previous studies have suggested that melatonin (MLT) acts directly on rat Leydig cells by modulating androgen production. In the present study, the site of action of MLT was investigated. The binding of 2-[125I]iodomelatonin (125I-MLT; 7-240 pmol/l) to Leydig cell membrane fragments was tested in the presence or absence of guanosine 5'-O-(3-thiotriphosphate) (GTP-gamma-S; 50 mumol/l). Saturation studies and Scatchard analysis revealed the existence of a high-affinity binding site with a Bmax of 46.70 +/- 3.50 fmol/mg protein and a Kd of 88.70 +/- 6.20 pmol/l; treatment with GTP-gamma-S reduced the concentration of 125I-MLT binding sites (Bmax 34.03 +/- 4.50), while increasing the Kd to 106.5 +/- 2.61 pmol/l. Pretreatment of the cells with pertussis toxin (PTX; 10 ng/ml for 16 h) resulted in a decreased binding of 125I-MLT and a lack of effect of GTP-gamma-S. Moreover, the effect of MLT on testosterone secretion induced by LH (30 mIU/ml), forskolin (1 mumol/l) and LHRH (100 nmol/l) was studied after 3-h incubation of cells which had been precultured with or without PTX. The inhibition of testosterone secretion due to MLT administration was eliminated by PTX pretreatment during forskolin and LH, but not during LHRH administration. However, 17-hydroxyprogesterone levels were higher in all groups incubated in the presence of MLT, irrespective of PTX pretreatment. Our data suggest that: (a) MLT receptors are present on the membranes of adult rat Leydig cells; (b) they couple through PTX-sensitive G-protein-coupled binding sites; (c) the mechanism by which MLT blocks 17-20 desmolase enzymatic activity (thus leading to increased 17-hydroxyprogesterone levels), and testosterone secretion during LHRH stimulation is likely to depend on one or more different mechanism(s) of action.
...
PMID:Melatonin receptors are present in adult rat Leydig cells and are coupled through a pertussis toxin-sensitive G-protein. 922 28


1 2 3 Next >>

---