Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0043167 (pertussis)
 19,595 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of pertussis toxin on the responses of rat pituitary-tumour (GH) cells to thyrotropin-releasing hormone (thyroliberin, TRH) were examined. Treatment of cells with pertussis toxin did not alter the affinity or concentration of TRH receptors, or the sensitivity of the TRH receptor to inhibition by guanine nucleotides. TRH caused an increase in low-Km GTPase activity in membrane-containing fractions from both control and pertussis-toxin-treated cells. TRH stimulation of inositol phosphate formation was insensitive to pertussis toxin. TRH caused a biphasic increase in the concentrations of cytosolic free Ca2+ as monitored by intracellularly trapped Quin 2, and this increase was the same in control and toxin-treated cultures. The toxin did not alter the increase in prolactin and growth-hormone (somatotropin) release stimulated by TRH or shift the TRH dose-response curve, and it did not affect the TRH-induced rise in prolactin synthesis measured over 24 h. However, pertussis toxin did block the ability of somatostatin and muscarinic agonists to inhibit prolactin and growth-hormone secretion stimulated by vasoactive intestinal peptide when analysed under the same conditions as those in which the TRH system was unaffected. These data indicate that the guanine nucleotide effects on TRH binding and activity are not mediated by Ni, but possibly by another member of the family of guanine-nucleotide-dependent regulatory proteins.
 ...
PMID:Thyroliberin action in pituitary cells is not inhibited by pertussis toxin. 302 9

The D2 dopamine agonist, bromocriptine, has been used as treatment for human PRL-secreting pituitary adenomas. The result of bromocriptine treatment is often a substantial reduction of tumor mass, suggesting that the dopamine agonist is acting as an antiproliferative agent. This action can be observed with a clonal pituitary tumor cell line. The agonist activation of the D2 dopamine receptor inhibits the growth of GH4ZR7 cells, a GH4C1 cell line stably transfected with the cDNA encoding the short form of the D2 dopamine receptor. This effect of dopamine was not sensitive to overnight treatment with 100 ng/ml pertussis toxin. Treatment of GH4ZR7 cells with the phorbol ester 4 beta-phorbol 12,13-didecanoate resulted in the loss of dopaminergic inhibition of growth, whereas treatment with 4 alpha-phorbol 12,13-didecanoate had no effect. Inhibitors of protein kinase-C (PKC), such as staurosporine and H7, also blocked the effect of dopamine. Down-regulation of cellular PKC by phorbol ester treatment resulted in a complete loss of dopaminergic inhibition of growth. Long term treatment of GH4ZR7 cells with TRH results in a specific down-regulation of the epsilon form of PKC and abolished the ability of dopamine to inhibit growth. These results suggest that PKC epsilon is involved in mediating the antiproliferative effects of dopamine. This mediation of growth appears to be through a novel signaling pathway for the D2 dopamine receptor.
 ...
PMID:The D2 dopamine receptor mediates inhibition of growth in GH4ZR7 cells: involvement of protein kinase-C epsilon. 750 37

The mechanisms of somatostatin (SRIH) action on thyroid-stimulating hormone (TSH) secretion were examined using human TSH-secreting adenoma cells. SRIH (10(-7) M) inhibited TSH secretion through a pertussis toxin-sensitive G protein. SRIH also inhibited forskolin- and 8-bromo-adenosine 3',5'-cyclic monophosphate (8-BrcAMP)-induced TSH secretion. The mechanisms of this inhibition were investigated by measuring intracellular Ca2+ concentration ([Ca2+]i) and by electrophysiological experiments. Application of 10(-7) M SRIH reduced the [Ca2+]i, whereas forskolin and 8-BrcAMP increased the [Ca2+]i. Simultaneous application of SRIH abolished the forskolin-and the 8-BrcAMP-induced [Ca2+]i increase, indicating that the SRIH-induced decrease in [Ca2+]i was independent of the reduction in intracellular cAMP. Under current clamp using the whole cell clamp, 10(-7) M SRIH hyperpolarized the membrane and arrested Ca(2+)-dependent action potentials, which accounted for the SRIH-induced decrease in [Ca2+]i. Voltage clamp experiments revealed that this membrane hyperpolarization resulted from the activation of an inward-rectifying K+ current through a pertussis toxin-sensitive G protein. Intracellular injection of cAMP (100 microM) through the patch pipette did not abolish the SRIH-induced K+ current, indicating that the activation of SRIH-induced K+ channels was independent of intracellular cAMP. From these data, we concluded that SRIH-induced membrane hyperpolarization was responsible for the [Ca2+]i decrease, which in turn inhibited TSH secretion. Application of thyrotropin-releasing hormone (TRH; 10(-7) M) caused an increase in the [Ca2+]i, composed of an initial transient increase followed by a sustained increase. SRIH inhibited the sustained increase in [Ca2+]i. SRIH also inhibited the TRH-induced decrease in the membrane conductance.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Mechanisms of action of somatostatin on human TSH-secreting adenoma cells. 773 52

This study examines the relation between inositol phosphate (IP) production and PRL release in four GGH3 cell lines (GGH(3)1', GGH(3)2', GGH(3)6', and GGH(3)12'; lactotropic GH3 cells that have been stably transfected with rat GnRH receptor complementary DNA). Production of IPs is an early response of GGH3 cells to a GnRH agonist, measurable at 15-30 min and maximal at 60 min after treatment with Buserelin in [3H]inositol preloaded cells. In contrast, PRL release, which requires protein synthesis, is not measurable until 1-3 h and total cAMP production is not measurable until about 24 h (3). In one of the lines studied (GGH(3)2'), PRL was also released in response to TRH. Measurable expression of the PRL gene requires 1-2 days (2). All four lines produced IPs robustly after treatment with Buserelin, although the IP response to TRH is minimal in all lines, being the best in the GGH(3)2' line. Pretreatment of cells with cholera toxin (CTX) or pertussis toxin (PTX) attenuated TRH-induced IP production in GGH(3)1', GGH(3)2', or GGH(3)12' cells. No effect of CTX or PTX is measurable in GGH(3)6' cells in terms of TRH stimulation of IP production. In contrast, both toxins augment Buserelin-stimulated IP production in GGH(3)1' and GGH(3)6' cells, but have no action in the other two lines. Both CTX and PTX inhibit Buserelin-stimulated PRL production. This study suggests that IP production is the earliest measurable response of GGH3 cells to a GnRH agonist, although this event does not appear to be coupled to Buserelin-stimulated PRL release. Further, the studies with toxins suggest that Buserelin and TRH appear to regulate IP production by different mechanisms.
 ...
PMID:Gonadotropin-releasing hormone (GnRH)-receptor coupling to inositol phosphate and prolactin production in GH3 cells stably transfected with rat GnRH receptor complementary deoxyribonucleic acid. 795 44

Recent findings indicate that low concentrations of dopamine (DA) stimulate the secretion of prolactin (PRL) in vitro. In this study, we found that low concentrations of the highly-specific DA D2 receptor agonist, quinpirole hydrochloride (LY) stimulate PRL secretion in female rats, assessed by reverse hemolytic plaque assay. Low concentrations of LY (10(-12), 10(-10) M) increased the mean plaque area and increased the fraction of lactotrophs forming large plaques. On the other hand, higher concentrations of LY (10(-8), 10(-6) M) reduced the mean plaque size. Treatment of cells with 10(-6) M LY produced a unimodal distribution of small plaques. Low concentrations of LY (10(-12), 10(-10) M) with TRH (10(-7) M) produced an additive effect on TRH-induced PRL release. Pretreatment of anterior pituitary cells with pertussis toxin (30 ng/ml, 24 h) inhibited the LY-stimulated increase in plaque area. These findings indicate that very low concentrations of DA agonist stimulate the secretion of PRL per cell, and that the stimulatory effects of DA agonist on PRL secretion may be mediated by a pertussis toxin-sensitive G protein.
 ...
PMID:The stimulatory and inhibitory effects of quinpirole hydrochloride, D2-dopamine receptor agonist, on secretion of prolactin as assessed by the reverse hemolytic plaque assay. 810 Sep 80

We studied the effect of adenosine on prolactin secretion by the anterior pituitary, and the transduction mechanisms whereby the purine exerts its action. Adenosine inhibited prolactin release in basal and in vasoactive intestinal peptide (VIP)- or TRH-stimulated conditions. Pertussis toxin pretreatment reduced the inhibition of VIP-stimulated prolactin secretion which was induced by adenosine, while it completely abolished the effect of the purine on TRH-evoked prolactin release. In membrane preparations of anterior pituitary cells, adenosine reduced the adenylate cyclase activity stimulated by VIP. Such an inhibition was not blocked by pertussis toxin pretreatment. Furthermore, the purine reduced TRH-stimulated inositol phosphate production in cultured anterior pituitary cells, an effect that was reversed by pretreatment with pertussis toxin. In addition, the nucleoside did not significantly affect the TRH-induced rise in intracellular calcium. In conclusion, our data show that adenosine inhibits prolactin secretion, acting on purinergic receptors coupled to the adenylate cyclase enzyme and phospholipase C. The effect of the nucleoside on adenylate cyclase seems to be achieved either by the involvement of an adenosine receptor coupled to the catalytic subunit of the enzyme via a pertussis toxin-sensitive G protein, or by the activation of a site directly coupled to the catalytic subunit of the adenylate cyclase (the P site). Its effect on phospholipase C seems to be mediated by a purinergic receptor coupled to the intracellular effector via a pertussis toxin-sensitive G protein.
 ...
PMID:Direct effect of adenosine on prolactin secretion at the level of the single rat lactotroph: involvement of pertussis toxin-sensitive and -insensitive transducing mechanisms. 814 40

The purpose of the experiments was to examine the behavior of cytosolic Ca2+ ([Ca2+]i) in individual pituitary melanotrophs and how that is affected by physiological ligands that inhibit or stimulate melanotroph secretion. Melanotrophs were dispersed from neurointermediate lobes of Xenopus laevis adapted to a black background, and [Ca2+]i was measured with fura-2. In basal (unstimulated) conditions, repetitive transient elevations in [Ca2+]i, not hitherto observed in any melanotrophs, were detected in 73% of the cells. These cytosolic Ca pulses occurred at fairly regular intervals (1-10 min) and lasted from a half to several minutes, during which [Ca2+]i rose several-fold. Pulsing was promptly and reversibly arrested by the secreto-inhibitory transmitters, dopamine, neuropeptide-Y (NPY), and gamma-aminobutyric acid (GABA), and also by quinpirole, muscimol, and baclofen. Pertussis toxin eliminated the responses to dopamine, NPY, and GABAB receptor activation, but spared responses to GABAA receptor activation. The responses to the physiological inhibitors and to the Ca channel blocker Ni were close to all or nothing; a mere doubling of an ineffective concentration commonly sufficed to arrest pulsing. Submaximal responses, seen over a narrow concentration range, involved a slowing of the pulsing. Cells not pulsing spontaneously were responsive to dopamine, GABA, and NPY and pulsed in response to the secretagogues CRF and TRH. They are suggested to be melanotrophs not actively secreting. The behavior of [Ca2+]i parallels secretory activity and strengthens the view that spontaneous secretion is driven by spontaneous influx of Ca ions and that secreto-inhibitory transmitters act by suppressing this influx and lowering [Ca2+]i. Cytosolic Ca pulsing may provide an efficient means of sustaining a high rate of spontaneous secretion.
 ...
PMID:Spontaneous cytosolic calcium pulsing detected in Xenopus melanotrophs: modulation by secreto-inhibitory and stimulant ligands. 838 13

The presence of the pertussis toxin (PTX) insensitive GTP-binding proteins (C-proteins) G(q) alpha and/or G(11) alpha has been demonstrated in three different prolactin (PRL) and growth hormone (GH) producing pituitary adenoma cell lines. Immunoblocking of their coupling to hormone receptors indicates that G(q) and/or G(11) confer throliberin (TRH) responsive phospholipase C (PL-C) activity in these cells. The contention was substantiated by immunoprecipitation analyses showing that anti G(q)/11 alpha-sera coprecipitated PL-C activity. In essence, only G(q)/11 (but neither G(12) G(13) nor G(o)) seems to mediate the TRH-sensitive PL-C activity, while G(o) may be coupled to a basal or constitutive PL-C activity. Immunoblocking studies imply that the B gamma-complex also, to some extent, may stimulate GH(3) pituitary cell line PL-C activity. Finally, the steady state levels of G(q)/(11) alpha mRNA and protein were down regulated upon long term exposure of the GH(3) cells to TRH (but not to vasoactive intestinal peptide = VIP).
 ...
PMID:Phospholipase C activation in rat pituitary adenoma (GH) cells. 886 41

TRH and somatostatin (SRIH) are well known to stimulate and to inhibit TSH secretion respectively. However, the mechanisms underlying the effect of SRIH on thyrotrophs are still not understood. We have previously shown in vitro that the TSH response to TRH is potentiated in a Ca(2+)-dependent fashion through the activation of dihydropyridine (DHP)-sensitive Ca2+ channels by the prepro-TRH (160-169) cryptic peptide (PS4) and tri-iodo-L-thyronine (T3), when the hormone was added shortly before a TRH pulse in order to avoid its genomic effect. Using perifused rat pituitary fragments, the present study has shown that SRIH inhibits, in a dose-dependent manner, the TSH response to physiological concentration of TRH (10 nM) and reverses the Ca(2+)-dependent potentiation of that response induced either by PS4 or by T3. We have also demonstrated that the inhibition by SRIH of the T3 potentiation of TRH-induced TSH secretion is pertussis toxin-sensitive. Our data suggest that SRIH inhibits the PS4 and T3 potentiation of TRH-induced TSH secretion through the inactivation of DHP-sensitive Ca2+ channels. Using primary cultures of rat anterior pituitary cells and videomicroscopy, we have already demonstrated that TRH, as well as PS4 and T3, are able to increase intracellular Ca2+ concentration ([Ca2+]i) rapidly, in 15 s. Our study has shown that SRIH is able to abolish the acute rise in [Ca2+]i induced either by PS4 or by T3. Since [Ca2+]i responses to PS4 and T3 are also abolished by the DHP nifedipine, our results suggest that [Ca2+]i changes in PS4- or T3-sensitive pituitary cells depend directly or indirectly on the activation of DHP-sensitive Ca2+ channels and that the inhibitory effect of SRIH may be mediated by inactivation of this type of channel.
 ...
PMID:Somatostatin blocks the potentiation of TRH-induced TSH secretion from perifused pituitary fragments and the change in intracellular calcium concentrations from dispersed pituitary cells elicited by prepro-TRH (PS4) or by tri-iodothyronine. 927 64

In CHO cells transfected with the rat dopamine D2 receptor (long isoform), administration of dopamine per se elicited a concentration-dependent increase in arachidonic acid (AA) release. The maximal effect was 197% of controls (EC50=25 nM). The partial D2 receptor agonist, (-)-(3-hydroxyphenyl)-N-n-propylpiperidine [(-)-3-PPP], also induced AA release, but with somewhat lower efficacy (maximal effect: 165%; EC50=91 nM). The AA-releasing effect of dopamine was counteracted by pertussis toxin, by the inhibitor of intracellular Ca2+ release, 8-(N N-diethylamino)octyl-3,4,5-trimethoxybenzoate (TMB-8), by excluding calcium from the medium, by the phospholipase A2 (PLA2) inhibitor, quinacrine, and by long-term pretreatment with the phorbol ester, 12-O-tetradecanoylphorbol-13-acetate (TPA). In addition, it was antagonized by the D2 antagonists, raclopride and (-)-sulpiride--but not by (+)-sulpiride--and absent in sham-transfected CHO cells devoid of D2 receptors. The results obtained contrast to the previous notion that dopamine and other D2 receptor agonists require the concomitant administration of calcium-mobilizing agents such as ATP, ionophore A-23187 (calcimycin), thrombin, and TRH, to influence AA release from various cell lines.
 ...
PMID:Direct dopamine D2-receptor-mediated modulation of arachidonic acid release in transfected CHO cells without the concomitant administration of a Ca2+-mobilizing agent. 975 80


<< Previous 1 2 3 4 Next >>