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)

Bordetella pertussis synthesizes a variety of virulence factors including a calmodulin-dependent adenylate cyclase (AC) toxin. Treatment of anterior pituitary cells with this AC toxin resulted in an increase in cellular cAMP levels that was associated with accelerated exocytosis of growth hormone (GH), prolactin, adrenocorticotropic hormone (ACTH), and luteinizing hormone (LH). The kinetics of release of these hormones, however, were markedly different; GH and prolactin were rapidly released, while LH and ACTH secretion was more gradually elevated. Neither dopamine agonists nor somatostatin changed the ability of AC toxin to generate cAMP (up to 2 h). Low concentrations of AC toxin amplified the secretory response to hypophysiotrophic hormones. We conclude that bacterial AC toxin can rapidly elevate cAMP levels in anterior pituitary cells and that it is this response that explains the subsequent acceleration of hormone release.
 ...
PMID:Prokaryotic adenylate cyclase toxin stimulates anterior pituitary cells in culture. 301 20

Acetylcholine is known to stimulate the secretion of growth hormone and prolactin and the efflux of 86Rb from bovine anterior pituitary cells: dopamine prevents the stimulation of 86Rb efflux and of prolactin but not growth hormone secretion. The sensitivity of these responses to pertussis toxin has been determined. Treatment of bovine anterior pituitary cells in primary culture with pertussis toxin (18 h, 100 ng/ml) did not modify the stimulation of prolactin secretion by acetylcholine, but prevented its inhibition by dopamine. In lactotrophs, dopamine but not acetylcholine receptors are therefore coupled to secretion through a pertussis toxin substrate. The stimulation of 86Rb efflux by acetylcholine was also unaffected by pertussis toxin and, again, its inhibition by dopamine was prevented. Treatment of the cells with pertussis toxin enhanced the secretion of growth hormone in response to acetylcholine. Nitrendepine (1 mumol/l) prevented the cholinergic stimulation of growth hormone but not prolactin secretion from these cells. Acetylcholine increased the cytoplasmic calcium concentration and this rise was enhanced by treatment of the cells with pertussis toxin. Nitrendepine partially inhibited the rise in calcium caused by acetylcholine, and prevented the enhancement of the rise following pertussis toxin treatment. Cholinergic stimulation of growth hormone therefore depends on calcium entry through nitrendepine-sensitive channels, whereas stimulation of prolactin secretion does not, and in somatotrophs a pertussis toxin substrate may limit calcium entry through these channels. These different sensitivities of somatotrophs and lactotrophs to pertussis toxin and nitrendepine may reflect differences in the properties of the predominant calcium currents in the two cell types.
 ...
PMID:Modification by pertussis toxin of the responses of bovine anterior pituitary cells to acetylcholine and dopamine: effects on hormone secretion and 86Rb efflux. 335 28

Pertussis toxin, cholera toxin and forskolin, all of which can increase adenylate cyclase activity, stimulated luteinizing hormone LH release from cultured rat anterior pituitary cells. Although cellular cyclic AMP and growth hormone were increased rapidly by cholera toxin and forskolin, enhanced LH release occurred significantly later with no change in total radioimmunoassayable LH (i.e., released plus stored). These data suggest that changes in cyclic AMP levels may regulate the tonic availability of releasable LH in the gonadotroph.
 ...
PMID:Luteinizing hormone secretion is enhanced by pertussis toxin, cholera toxin, and forskolin. Evidence for the involvement of the cyclic AMP-generating system. 631 Apr 32

Somatostatin regulates endocrine and exocrine secretion, possesses antiproliferative properties and acts as a neurotransmitter/neuromodulator in the central nervous system. These effects are mediated by G protein-coupled receptors, of which at least five types have been cloned (sstr1-5). In radioligand-binding studies we have compared the binding properties of sstr1-5 with their activities as somatostatin receptors. All receptors identified so far bind somatostatin-14 and somatostatin-28 with high affinity. The similarities in receptor sequence and in the binding profiles of short synthetic somatostastin analogues such as octreotide, MK 678 or RC 160 for sstr1-5 indicate the existence of two classes of receptors sstr1/sstr4 with virtually no or very low affinity and sstr2/sstr3/sstr5 with intermediate to high affinity for the short somatostatin analogues. All five receptors mediate inhibition of adenylyl cyclase; this inhibition is sensitive to pertussis toxin. In vitro and in vivo studies suggest the importance of sstr2 and/or sstr5 in the inhibition of growth hormone release. The sstr2 receptor is apparently the predominant subtype expressed in somatostatin receptor-positive tumours. Evidence exists for the importance of sstr5 receptors in insulin secretion and sstr1 receptors in oncology. Somatostatin receptor-selective agonists and antagonists will help to explore new therapeutic opportunities in oncology as well as in endocrine and gastrointestinal disorders and those of the central nervous system.
 ...
PMID:Characterization of somatostatin receptor subtypes. 758 55

Dopamine (DA) inhibited the secretion of growth hormone (GH) from cultured human GH-secreting adenoma cells. The mechanism of this DA effect on these cultured cells was investigated with electrophysiological techniques. Under current clamp, DA (10(-6) M) hyperpolarized the membrane and arrested Ca(2+)-dependent action potentials. Voltage clamp experiments revealed that this membrane hyperpolarization was the result of a K+ conductance increase caused by DA. The current-voltage relationship of the DA-induced K+ current showed an inward-going rectification. Application of sulpiride (10(-6) M) abolished the DA-induced K+ current, indicating that the hyperpolarization was caused by the activation of D2-like receptors. Pertussis toxin (PTX) treatment eliminated the DA-induced K+ current as well as the DA-induced inhibition of GH secretion. An intracellular application of guanosine-5'-O-(3-thiotriphosphate) (100 microM) evoked a spontaneous increase in the K+ current in the absence of an agonist, and the application of DA did not further increase conductance. Intracellular application of guanosine-5'-O-(2-thiodiphosphate) (2 mM) inhibited the DA-induced K+ current. These results indicate that the DA-induced K+ channel is coupled to a G protein. When adenosine 3',5'-cyclic monophosphate (cAMP, 100 microM) was added to the patch-pipette solution, the DA-induced K+ current was still observed, indicating that the DA-induced K+ current was not caused by an inhibition of cAMP production.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Activation of G protein-coupled K+ channels by dopamine in human GH-producing cells. 790 7

Cortisol inhibits growth hormone (GH) release in short-term culture and is stimulatory in long-term cultures of rat and human pituitary cells. This study sought to determine the in vitro effects of cortisol on GH release and the signal transduction pathways mediating the effects of cortisol on GH release from cultured ovine somatotrophs. Pituitary cells were dispersed with collagenase and placed in culture medium for 4 days. The data indicate that cortisol inhibited growth hormone-releasing hormone (GHRH)-stimulated GH release by at least 2 h. In short-term culture GHRH-, forskolin- and dibutyryl cyclic AMP-stimulated GH release were inhibited by cortisol, suggesting an effect distal to the membrane and involving a protein kinase A (PKA)-dependent pathway. GH release initiated by KCl was inhibited by cortisol, but GH release caused by the calcium ionophore A23187 was unaffected. This suggests a possible action of cortisol on the calcium channels. The inhibition by cortisol of the calcium-dependent secretion of GH release appeared to play a smaller role in mediating cortisol inhibition of GH release than that seen with PKA. Attempts to overcome cortisol inhibition of GH release using puromycin, arachidonic acid or pertussis toxin were unsuccessful. Since cortisol inhibition of GH release does not occur via the mechanisms found in other cell types, cortisol inhibition of pituitary cell secretions appears to be cell-specific rather than utilizing a single inhibitory mechanism. The majority of cortisol actions on the somatotroph appear to act at a site distal to the production of cyclic AMP.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Cortisol inhibition of growth hormone-releasing hormone-stimulated growth hormone release from cultured sheep pituitary cells. 807 50

Interleukin-6 (IL-6) was secreted by cultured cells of 7 out of 11 human pituitary adenomas that were examined. Interleukin-1 (IL-1) stimulated IL-6 release after a 24-h incubation period in five of the seven IL-6-secreting adenoma cultures and in all seven after 72 h. Tumour necrosis factor, interferon-gamma and epidermal growth factor did not significantly affect IL-6 secretion. Interleukin-1 failed to induce measurable IL-6 in the cultures that did not secrete IL-6 under basal conditions. Prostaglandin E2 did not influence basal IL-6 secretion and indomethacin did not inhibit IL-1-stimulated IL-6 release. In addition, pertussis toxin had no effect on IL-1-stimulated IL-6 release. The growth hormone (GH) secretory response to IL-1 varied, with stimulation in one GH-secreting adenoma culture, no significant effect in a second and inhibition in a third. Interleukin-1 did not significantly affect the release of prolactin, thyrotrophin, luteinizing hormone or follicle-stimulating hormone in any of the adenoma cultures. This study provides evidence that IL-1 is a stimulator of IL-6 release from cultured human pituitary adenoma cells that secrete IL-6. Stimulation of IL-6 release by IL-1 in these tumour cells is probably not mediated by prostaglandins or by a pertussis toxin-sensitive mechanism.
 ...
PMID:Interleukin-1 stimulates the release of interleukin-6 from cultured human pituitary adenoma cells. 839 Nov 94

It is known that withdrawal of somatostatin (SRIF) augments the growth hormone (GH) releasing hormone (GRF)-induced GH secretion. To investigate the mechanism of this augmentation in GH secretion, effects of GRF and SRIF on L-type Ca2+ current (Ba2+ was used as a charge carrier) or primary cultured rat somatotroph were studied by perforated patch clamp technique. The reason is that GRF-induced GH secretion is thought to be causally related to the influx of Ca2+ through L-type Ca2+ channels. 10 mM GRF augmented maximum amplitude of L-type Ba2+ current by 12.2% (n = 12). Subsequent application of SRIF slightly suppressed the currents but the suppression never exceeded the control level of the current. Removal of SRIF, however, promptly augmented the L-type Ba2+ current by 26.8%. Such off-response of SRIF was not observed in cells treated overnight with 100 ng/ml pertussis toxin. Further, specific inhibitor of protein kinase A, H-89 at 1 microM reversibly suppressed the augmentation of L-type Ba2+ current to control level. At 10 microM, H-89 suppressed L-type Ba2+ current by more than 40% from control level. These results suggest that (1) L-type Ca2+ channel of somatotroph is probably phosphorylated in a basal condition and may be slightly modulated by GRF through increased level of cAMP; (2) SRIF only slightly suppress the channel activity; (3) Withdrawal of SRIF facilitates the activity of L-type Ca2+ channel via PTX-sensitive G-protein, although the precise mechanism of this facilitation is unknown. The augmentation by SRIF-pretreatment of GRF-induced GH secretion may be at least partly due to the facilitation of the activity of L-type Ca2+ channel.
 ...
PMID:Withdrawal of somatostatin augments L-type Ca2+ current in primary cultured rat somatotrophs. 874 22

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

Chronic exposure of sheep adipose tissue to growth hormone (GH) in vitro decreases the ability of the adenosine analogue, N6-phenylisopropyladenosine (PIA), to inhibit isoprenaline-stimulated lipolysis by a mechanism which is dependent on both gene transcription and protein serine/threonine phosphorylation. The inhibition is not due to a change in ligand binding to the adenosine receptor, the amounts of the three isoforms of the inhibitory GTP-binding protein, Gi, or the maximum (forskolin-stimulated) adenylate cyclase activity. The ability of GH to modulate the PIA-activated adenosine receptor to stimulate dissociation of heterotrimeric Gi was assessed by measurement of pertussis toxin-catalysed ADP-ribosylation of Gi; GH does not appear to alter the interaction between the activated receptor and Gi. The ability of GH to alter the ability of activated Gi to inhibit adenylate cyclase activity was assessed by measuring the ability of a GTP analogue, guanosine 5'-[beta gamma-imido]triphosphate (p[NH]ppG), to inhibit forskolin-stimulated adenylate cyclase activity; chronic exposure to GH prevented this effect of p[NH]ppG. Thus the attenuation of the inhibition of lipolysis by PIA by chronic exposure of adipocytes to GH appears to be due to an impairment in the interaction between adenylate cyclase and the alpha subunit of one or more isoforms of Gi.
 ...
PMID:Regulation of the GTP-binding protein-based antilipolytic system of sheep adipocytes by growth hormone. 984 58


<< Previous 1 2 3 4 Next >>