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)

The 7315c cell, derived from a rat anterior pituitary tumor, expresses an angiotensin II (AII) receptor. [3H]AII binds to 7315c membranes specifically and saturably (Kd = 2.1 +/- 0.6 x 10(-6) M, Bmax = 282 +/- 33 fmol/mg of protein). GTP diminished the affinity of the membranes for [3H]AII (Kd = 4.1 +/- 0.4 x 10(-9) M, Bmax = 210 +/- 26 fmol/mg of protein). [3H]AII binding was displaced by AII (Ki = 1.3 +/- 0.6 x 10(-9) M), angiotensin III (AIII) (Ki = 0.9 +/- 0.4 x 10(-9) M), and the nonpeptide AII antagonist DuP753 (Ki = 1.4 +/- 0.6 x 10(-8) M). In contrast, a second nonpeptide AII ligand, PD123177, did not compete for [3H]AII binding sites. In intact cells, AII and AIII stimulated inositol trisphosphate (IP3) production (EC50 = 1.1 +/- 0.6 x 10(-8) M and 1.1 +/- 0.5 x 10(-8) M, respectively); this response to AII was antagonized by DuP753 (Ki = 1.7 +/- 0.3 x 10(-7) M). Pertussis toxin treatment failed to affect the ability of AII to stimulate IP3 production. In a crude membrane preparation, GTP was required for maximal AII-induced IP3 stimulation; guanosine thio-diphosphate abolished the agonist-GTP stimulation of IP3 production, in a concentration-dependent fashion. AII and AIII also inhibited adenylyl cyclase (EC50 = 2.9 +/- 1.1 x 10(-8) M and 6.0 +/- 1.0 x 10(-8) M, respectively). DuP753 antagonized the inhibition by AII of adenylyl cyclase (Ki = 2.8 +/- 0.4 x 10(-8) M). PD123177 failed to antagonize AII-induced cyclase inhibition. Pertussis toxin treatment abolished the AII and AIII inhibition of adenylyl cyclase. GTP was required for AII-induced inhibition of adenylyl cyclase. These data suggest that, in 7315c cells, a single subtype of AII receptor, identified by DuP753, is capable of regulating two different guanine nucleotide-binding protein (G protein) signalling pathways; one G protein, which is insensitive to pertussis toxin, stimulates IP3 production and the other G protein, which is sensitive to pertussis toxin, inhibits adenylyl cyclase.
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PMID:Angiotensin II receptor recognized by DuP753 regulates two distinct guanine nucleotide-binding protein signaling pathways. 131 Jan 39

The somatostatin (SS) analog octreotide has been successfully used in the treatment of (neuro)endocrine tumors. The mechanism of action of the tumor (growth) inhibitory action by octreotide is not fully understood. We have investigated the effect of octreotide on 7315b rat pituitary tumor cell growth, PRL release, and intracellular PRL concentrations in vitro. When cultured in medium with 10% fetal calf serum, the number of high affinity SS receptors increased with increasing culture time. On days 7, 14, and 21 of culture, the number of SS receptors amounted to 978 +/- 217, 3588 +/- 705, and 5865 +/- 3332 fmol/mg protein, respectively, whereas they were not measurable on day 0. From days 0-7, 7-14, and 14-21 of culture, octreotide (1 pM to 1 microM) inhibited PRL release and the intracellular PRL concentration, with IC50 values in the nanomolar range. However, no inhibition of cell growth was observed by these octreotide concentrations from day 0-7 of culture, while octreotide inhibited cell growth in a dose-dependent fashion from days 7-14 and 14-21 of culture (maximal inhibition by 25% and 26%, respectively). In a series of nine consecutive experiments we found a significant positive correlation between the percent inhibition of cell growth induced by 1 microM octreotide and the number of SS receptors on 7315b cells (r = 0.7865; P = 0.012). Inhibition of PRL release did not correlate with SS receptor numbers. Octreotide (1 microM) inhibited forskolin (0.5 microM)-stimulated cell growth and intracellular PRL concentrations, while in the presence of a high concentration of forskolin (10 microM), octreotide had no effect on forskolin-stimulated cell growth and intracellular PRL concentrations. In addition, its PRL release inhibitory effect was significantly lower in forskolin-stimulated cultures. Pretreatment of the cells with pertussis toxin (10 micrograms/liter) completely prevented the inhibition of cell growth by octreotide and diminished the inhibitory effect of octreotide on PRL release. Finally, 1 microM octreotide significantly inhibited forskolin-stimulated cAMP production (by 29% and 53% on days 7 and 14 of culture, respectively). We conclude that 1) octreotide inhibits 7315b rat pituitary tumor cell proliferation via a pertussis toxin-sensitive GTP-binding protein- and adenylate cyclase-dependent mechanism; and 2) the number of SS receptors on 7315b pituitary tumor cells may determine whether octreotide exerts a direct antiproliferative effect, whereas its antihormonal effect occurs in the presence of relatively low numbers of SS receptors. This suggests a dissociation of the antiproliferative and antihormonal effects induced by octreotide.
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PMID:Dissociation of antiproliferative and antihormonal effects of the somatostatin analog octreotide on 7315b pituitary tumor cells. 132 74

1. The patch-clamp technique was used to study the action of the beta-adrenergic agonist (-)-isoproterenol in anterior pituitary tumor cells of the mouse. 2. (-)-Isoproterenol induced an inward-rectifying potassium conductance with half-maximal stimulation at a concentration of approximately 67 nM. The isomer (+)-isoproterenol was less effective in stimulating the current. 3. The effect of (-)-isoproterenol was abolished by cholera toxin treatment, indicating the involvement of a Gs protein, whereas pertussis toxin treatment did not exhibit a current reduction. 4. We blocked or stimulated phosphorylation pathways in cells to test the involvement of adenosine 3',5'-cyclic monophosphate (cAMP). It was concluded that the current stimulation probably was not exclusively mediated by cAMP. 5. Activation of calcium-dependent potassium channels by an isoproterenol-induced calcium influx into the cell could be excluded. 6. Therefore it is suggested that the observed activation of a potassium current by isoproterenol could be directly mediated by a Gs protein.
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PMID:Isoproterenol enhances a calcium-independent potassium current in mouse anterior pituitary tumor cells. 151 18

In past studies we observed that the chloride channel blocker, diphenylamine-2-carboxylate (DPC) and chemically related drugs (Hoechst compounds 131, 143, 144) inhibited cAMP formation in mouse pituitary tumor cells. The object of this study was to determine whether these drugs inhibited chloride transport in human T-84 colonic carcinoma cells through an effect on cAMP metabolism. Chloride secretion (measured as 125I efflux from isotope-preloaded cells) was stimulated in a concentration-dependent manner by vasoactive intestinal polypeptide (VIP) (EC50 = 1.5 x 10(-10) M) which similarly increased cAMP synthesis (EC50 = 1.6 x 10(-8) M). The cAMP response to VIP was inhibited 17, 52, 55, and 78% maximally by DPC and compounds 144, 143, and 131, respectively. In untreated T-84 cells, 125I secretion fell by 66% after 3 min; VIP (10(-7) M) increased secretion about fivefold over the same period. Both basal and VIP-stimulated 125I secretion were inhibited up to 60% by compound 131. Pretreatment of cells with pertussis toxin did not attenuate the inhibitory effect of channel blockers on either VIP-stimulated cAMP synthesis or 125I secretion. The cationophore, A-23187, which had no effect on cAMP formation, and 8-Br-cAMP both stimulated 125I secretion from T-84 cells. These secretory responses were inhibited by compound 131. The mechanism by which phenylanthranilic acids antagonize cAMP synthesis and its significance is not known; however, the data suggest that this family of drugs may inhibit chloride transport by both cAMP-dependent and independent mechanisms.
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PMID:Antagonists of epithelial chloride channels inhibit cAMP synthesis. 164 53

We have examined the effect of acetylcholine (ACh) pretreatment on the thyrotropin-releasing hormone (TRH) induced prolactin gene expression in GH3 cells, a rat pituitary tumor cell line. Prolonged exposure (greater than 6 h) to ACh enhanced the TRH-induced prolactin mRNA accumulation in a time- and concentration-dependent manner while ACh by itself did not affect the basal prolactin mRNA levels appreciably. Maximal augmentation of the TRH-induced prolactin mRNA accumulation was obtained when cells were pretreated with 10(-5) M ACh for 24 h. The activation was mimicked by carbachol and oxotremorine and was blocked by the simultaneous presence of atropine. Preincubation of GH3 cells with pertussis toxin abolished the augmenting effect of ACh. These results indicate that prolonged exposure to muscarinic receptor agonists may enhance the TRH-stimulated prolactin mRNA expression and a pertussis toxin sensitive G-protein may be involved.
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PMID:Potentiation of thyrotropin-releasing hormone-stimulated prolactin mRNA levels in GH3 cells by acetylcholine. 176 Nov 64

A permanent line of cells has been established from the transplantable rat pituitary tumor 7315a. P11 cells have been cloned repeatedly, and after more than 60 passages their growth and characteristics are stable. Results of radioligand binding studies with 125I-lysergic acid diethylamide (125I-LSD) indicate that P11 cells express serotonin-2 (5-HT2) receptors. Analysis of the binding of 125I-LSD to membranes prepared from P11 cells revealed the presence of a single class of high affinity sites (Kd = 1.6 nM; Bmax = 211 fmol/mg of protein). The pharmacological profile of the inhibition of the binding of 125I-LSD by a panel of drugs was consistent with the expected profile of these drugs at 5-HT2 receptors. The affinity of the site for serotonin was in the low micromolar range and was decreased by GTP. Phosphoinositide hydrolysis in P11 cells, measured in the presence of lithium, was stimulated by serotonin. Increasing concentrations of the 5-HT2-selective antagonist ketanserin blocked phosphoinositide hydrolysis stimulated by serotonin, and Schild analysis was consistent with a simple competitive interaction. The Ki for ketanserin derived from Schild analysis was comparable to the Ki for ketanserin at the binding site for 125I-LSD. These results suggest that stimulation of phosphoinositide hydrolysis in P11 cells by serotonin is mediated by 5-HT2 receptors. Pretreatment of P11 cells with pertussis toxin caused ADP-ribosylation of Gi and Go, but did not affect the ability of serotonin to stimulate phosphoinositide hydrolysis. Therefore, the guaninine nucleotide-binding protein involved in the coupling of 5-HT2 receptors to phospholipase C in P11 cells is unlikely to be either Gi or Go. P11 cells expressing 5-HT2 receptors coupled to phosphoinositide hydrolysis will be a useful model system for future studies of the regulation and function of 5-HT2 receptors on cultured cells.
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PMID:Serotonin-2 receptors coupled to phosphoinositide hydrolysis in a clonal cell line. 216 57

The effect of pertussis toxin on somatostatin-induced K+ current was examined in dissociated human pituitary tumor cells obtained from two acromegalic patients. Somatostatin-induced hyperpolarization or K+ current was observed in 20 of 23 cells in adenoma 1 and 10 of 11 cells in adenoma 2. After treatment with pertussis toxin for 24 h, these responses were completely suppressed (0/14 in adenoma 1, 0/10 in adenoma 2). Spontaneous action potentials, K+, Na+, and Ca2+ currents were well preserved after pertussis toxin treatment. When crude membrane fraction was incubated with [32P]NAD, a 41K protein was ADP-ribosylated by pertussis toxin. Hormone release was inhibited by somatostatin and this inhibition was blocked by pertussis toxin treatment.
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PMID:Pertussis toxin inhibits somatostatin-induced K+ conductance in human pituitary tumor cells. 244 Mar 14

The role of protein kinase C in regulating Ca2+ channel activity was investigated using the whole-cell patch-clamp technique in the mouse pituitary tumor cell line AtT-20. The Ca2+ current was activated by depolarizing voltage steps from a holding potential of -80 mV. Extracellular application of the protein kinase C activator 1-oleoyl-2-acetylglycerol (OAG) reduced voltage-dependent Ca2+ current. This effect was reversible and dose dependent (10-100 microM). Pertussis toxin did not block the effect of OAG on Ca2+ current, suggesting that OAG does not affect Ca2+ channels via a pertussis toxin sensitive guanosine triphosphate binding protein. Na+-free solutions did not block the effect of OAG on Ca2+ channels, suggesting that this effect of OAG does not involve the Na+/H+ antiporter. The phorbol esters 12-deoxyphorbol-13-isobutyrate (10 microM) and phorbol-12,13-diacetate (100 microM) also reduced Ca2+ current. The results suggest that protein kinase C may be an inhibitory regulator of voltage-dependent Ca2+ channels.
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PMID:The protein kinase C activator 1-oleoyl-2-acetylglycerol inhibits voltage-dependent Ca2+ current in the pituitary cell line AtT-20. 244 24

In the present study we used 235-1 cells, a prolactin secreting clone derived from a pituitary tumor. In these cells maitotoxin, a calcium channels activator, likely acting on voltage sensitive calcium channels, increases intracellular free calcium measured by Quin 2 technique. Maitotoxin stimulation of calcium flux was inhibited both by nicardipine and verapamil in a dose dependent manner. Pertussis toxin pretreatment does not modify maitotoxin activation of calcium channels, while completely abolishes nicardipine inhibition of maitotoxin induced voltage sensitive calcium channels activation, without affecting verapamil effect. These results suggest a possible involvement of a pertussis toxin sensitive G protein in dihydropyridine inhibition of voltage sensitive calcium channels.
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PMID:Pertussis toxin pretreatment abolishes dihydropyridine inhibition of calcium flux in the 235-1 pituitary cell line. 245 May 38

The effects of prolonged morphine exposure on the mu opioid receptor in 7315c pituitary tumor cell membranes have been examined. Since a low concentration of naloxone reversed the inhibition of forskolin-stimulated adenylyl cyclase induced by the mu-selective agonist, Tyr-D-Ala-Gly-MePhe-Gly-ol (DAGO), and by high concentrations of [D-Pen2-D-Pen5]enkephalin (DPDPE), we suggest that these cells contain a homogeneous population of mu opioid receptors coupled to adenylyl cyclase via a guanyl nucleotide-binding protein. Studies measuring the ability of [D-Ala2-D-Leu5]enkephalin (DADLE), an opioid agonist, to inhibit adenylyl cyclase in cells that had been exposed to 100 microM morphine for varying periods of time, indicated that the agonist no longer inhibited enzyme activity after 5 hr of morphine exposure. Measurements of 3H-antagonist binding in membranes from cells exposed to morphine demonstrated a decreased receptor density after 24 hr of 100 microM morphine exposure with no change in the antagonist affinity. Computer analysis indicated a 20% decrease in the number of mu receptors labeled after 24 hr of morphine exposure and a 60% decrease after 72 hr of exposure. Computer analysis of agonist competition against 3H-antagonist binding confirmed the existence of one binding site with an affinity intermediate between the high and low apparent affinity states observed in membranes from untreated cells. Addition of 10 microM GTP gamma S did not affect the agonist affinity or receptor density in membranes from morphine-treated cells, suggesting that the receptors were uncoupled from G proteins, as observed in 7315c cell membranes that have been treated with pertussis toxin. Thus chronic morphine treatment induced a rapid loss of opioid mu receptor-mediated inhibition of adenylyl cyclase (desensitization), and a more slowly developing reduction in receptor number. The desensitization was accompanied by a loss of guanyl nucleotide regulation of agonist affinity. These findings are comparable to results reported for the delta opioid receptor and the beta-adrenergic receptor upon prolonged agonist exposure.
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PMID:Effects of chronic morphine exposure on opioid inhibition of adenylyl cyclase in 7315c cell membranes: a useful model for the study of tolerance at mu opioid receptors. 283 51


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