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

Two Ca(2+)-mobilizing receptors expressed in lactotrophs, endothelin-A (ET(A)) and thyrotropin-releasing hormone (TRH), induce a rapid Ca(2+) release from intracellular stores and prolactin (PRL) secretion but differ in their actions during the sustained stimulation; TRH facilitates and ET-1 inhibits voltage-gated calcium influx (VGCI) and PRL secretion. In pertussis toxin (PTX) treated cells, ET-1-induced inhibition of VGCI was abolished and the pattern of Ca(2+) signaling was highly comparable with that observed in TRH-stimulated cells. The addition of Cs(+), a relatively specific blocker of inward rectifier K(+) channels, mimicked the effect of PTX on the pattern of ET-1-induced sustained Ca(2+) signaling, but only in about 50% of cells, and did not affect agonist-induced inhibition of PRL secretion. Extracellular Cs(+) was also ineffective in altering the TRH-induced facilitation of VGCI and PRL secretion. Furthermore, apamin and paxilline, specific blockers of Ca(2+)-activated SKand BK-type K(+) channels, respectively; E-4031, a blocker of ether a-go-go K(+) channel; and linopirdine, a blocker of M-type K(+) channel, did not affect the agonist-specific patterns of calcium signaling and PRL secretion. These results suggest that ET-1 inhibits VGCI through activation of Cs(+)-sensitive channels, presumably the Gi/o-controlled inward rectifier K(+) channels, and that this agonist also inhibits PRL release, but downstream of Ca(2+) influx. Further studies are required to identify the mechanism of sustained TRH-induced facilitation of VGCI and PRL secretion.
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PMID:Dependence of prolactin release on coupling between Ca(2+) mobilization and voltage-gated Ca(2+) influx pathways in rat lactotrophs. 1266 67

We have shown previously that responses to lysophosphatidic acid (LPA) in Xenopus oocytes exhibit pronounced rapid homologous desensitization mediated by Go family of G-proteins (Itzhaki-Van Ham et al., 2004, J Cell Physiol, 200: 125-133). The present study was aimed at examining the involvement of Go G-proteins in rapid heterologous desensitization of native and expressed G-protein-coupled receptors in Xenopus oocytes. Threshold stimulation of the native lysophosphatidic acid receptors (LPA-Rs) induced about 50% rapid desensitization of responses evoked by stimulation of either native trypsin or expressed M1-muscarinic cholinergic receptors (M1-Rs). Similarly, threshold stimulation of expressed M1-Rs or thyrotropin-releasing hormone receptors induced 40% rapid desensitization of responses to LPA. Inactivation of all Gi/o G-proteins with pertussis toxin (PTX) completely abolished rapid heterologous desensitization in all protocols. Depletion of either Galphao or Galphao1 by antisense oligodeoxynucleotides targeted at either member of the Galphao family decreased or completely abolished rapid heterologous desensitization. Expression of two dominant negative mutants of the human Galphao family, highly homologous to oocyte Galphao species, either decreased or virtually abolished rapid desensitization. Homologous and heterologous desensitizations of the LPA response were non-additive and proceeded, apparently, via the same pathway. We conclude that Go G-proteins mediate both homologous and heterologous rapid desensitization of responses mediated by G-protein-coupled receptors (GPCRs) coupled to the phosphoinositide phospholipase C-inositol 1,4,5-trisphosphate-Ca(2+) (PI-PLC-InsP(3)-Ca(2+)) pathway in Xenopus oocytes.
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PMID:Go G-proteins mediate rapid heterologous desensitization of G-protein coupled receptors in Xenopus oocytes. 1579 22

Although the G-protein coupled receptor GPR10 is highly expressed in the anterior pituitary, the action of its ligand prolactin-releasing peptide-31 (PrRP) in this tissue is controversial. The present study examined the acute effect of this peptide on prolactin secretion in perifused rat pituitary reaggregate cell cultures from adult male rats. PrRP readily and dose-dependently stimulated prolactin release at concentrations of 10 and 100 nM, although with a magnitude several times lower than that of thyrotropin-releasing hormone. Surprisingly, PrRP inhibited prolactin release at 0.1 and 1 nm in a pertussis toxin-sensitive manner. Inhibition was markedly favoured by long-term culture. Stimulation and inhibition were differentially affected by the presence of hormones during culture: dexamethasone favoured the inhibitory effect and decreased the magnitude of the stimulatory effect, while oestradiol and triiodothyronine strongly reduced stimulation, as well as inhibition. PrRP, even at 1 nm, counteracted the inhibition of prolactin release by dopamine. There was no effect of PrRP on growth hormone release in aggregates cultured either in the absence or presence of hormones. The present results confirm the prolactin-releasing capacity of PrRP at nanomolar doses and reveal a hitherto unrecognized inhibitory activity of this peptide. Furthermore, dopamine inhibition of prolactin release is antagonized by PrRP, irrespective of the PrRP dose.
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PMID:Stimulation and inhibition of prolactin release by prolactin-releasing Peptide in rat anterior pituitary cell aggregates. 1592 43

Abstract The relative potencies of dopamine and somatostatin to inhibit prolactin secretion by pituitary cells in primary culture were compared. Hormone secretion was evaluated under basal conditions as well as after challenging it with thyrotropin-releasing hormone, vasoactive intestinal peptide or with drugs affecting either the activity of adenylate cyclase (forskolin), and protein kinase C (phorbol 12 myristate 13 acetate), or eliciting Ca(2) (+) fluxes in the cell by various ways (A23187, a Ca(2+) ionophore, the dihydropyridine agonist BAY-K-8644, or K(+) depolarization which activates voltage-sensitive Ca(2+) channels). In order to test whether all effects of dopamine and somatostatin were mediated by inhibitory guanosine triphosphate binding proteins, the experiments were systematically carried out in the presence or absence of pertussis toxin, an agent which selectively uncouples given subsets of G proteins from corresponding receptors. Dopamine markedly inhibited basal as well as thyrotropin-releasing hormone-, vasoactive intestinal peptide-, forskolin- and BAY-K-8644-stimulated release of prolactin. In contrast, dopamine was only able to induce partial inhibition of hormone release when secretion was triggered by tumour-promoting activator, A23187 or K(+) depolarization. Under all conditions tested, inhibition by somatostatin was significant, but of limited amplitude. Pertussis toxin completely reversed the effects of somatostatin. In contrast, complete reversal of dopamine effects by pertussis toxin was only achieved after hormone stimulation by tumour-promoting activator, alone or with A23187. Under all other conditions a residual dopamine inhibition was maintained in the presence of the toxin. The amplitude of this residual toxin resistant inhibition was comparable in all other cases to that observed for unstimulated (basal) prolactin release. It is concluded that: 1) As expected, dopamine is a potent inhibitor of secretory processes involving cyclic AMP accumulation or voltage-sensitive Ca(2+) channel activation. In contrast, the amine is only a partial inhibitor of exocytosis resulting from non-voltage-sensitive Ca(2+) channel-gated increase in Ca(2+) or direct activation of protein kinase C. 2) Somatostatin is a partial inhibitor of prolactin under all conditions tested. Dopamine and all somatostatin effects are mediated by pertussis toxin-sensitive G proteins. However, a small, but significant, proportion of dopamine inhibition is resistant to pertussis toxin and can thus be assumed to involve a distinct mode of action. This alternate mechanism of dopamine inhibition operates under all conditions except after treatment with tumour-promoting activator, suggesting that it can be inactivated by protein kinase C stimulation.
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PMID:Differential mechanisms of dopamine and somatostatin inhibition of prolactin secretion from anterior pituitary cells. 1921 42


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