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 modulatory role of protein kinase C (PK-C)- and Gi-protein-mediated signal transduction systems was studied in the cyclic variation of follicle-stimulating hormone (FSH)-stimulated cAMP production of rat seminiferous tubules. FSH (Metrodin, Serono, 30 mg/l) stimulated cAMP production 10-fold (p less than 0.01) in a 3 h incubation of 5 mm segments of seminiferous tubules of stages II-VI of the epithelial cycle, but only 2-fold (p less than 0.01) in stages VII-VIII. The PK-C activator 12-O-tetradecanoylphorbol 13-acetate (TPA, 100 nmol/l) suppressed the FSH effect on cAMP output by 50-70% (p less than 0.01) in stages II-VI, but had no effect in stages VII-VIII. If the tubular segments were preincubated for 3 h in the presence of pertussis toxin (PT, 100 micrograms/l), the FSH-stimulated cAMP production of stages VII-VIII increased by 100-200% (p less than 0.01), and now they also became responsive to the TPA suppression. Conversely, no effect of PT was observed in stages II-VI. Cholera toxin (CT, 100 micrograms/l) and forskolin (Fk, 100 mumol/l) nearly similarly stimulated the cAMP production in both stages studied (about 10-fold, p less than 0.01), and TPA and PT potentiated the effects in a non-additive fashion. In conclusion, both Gi-protein and PK-C-mediated mechanisms modulate cAMP production of rat seminiferous tubules. A clear cyclic variation can only be demonstrated in FSH-stimulated cAMP production, but not if the Gs-protein or adenylate cyclase are directly stimulated.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Protein kinase C and Gi-protein mediated modulation of cAMP production in different stages of the rat seminiferous epithelium. 216 36

Cyclic (c) AMP production was measured in vitro in dissected pieces of adult rat seminiferous tubules of defined stages of the seminiferous epithelial cycle (VII-VIII and XIV-IV) in the absence and presence of human follicle-stimulating hormone (FSH) (Metrodin, Serono). The basal rate of cAMP production was stage dependent, being about 2-fold higher in stages XIV-IV. FSH stimulated cAMP output in a time- and dose-dependent (stimulation at doses greater than or equal to 3 mg/l) fashion, and also the stimulability of stages XIV-IV (on average 2-fold) was greater than that of stages VII-VIII. When the tubular pieces were incubated in the presence of pertussis toxin (PT, 100 micrograms/l), the FSH-stimulated cAMP production of stages VII-VIII was enhanced by about 2-fold (P less than 0.01) whereas the basal rate was unaffected. In contrast, neither the basal nor the FSH-stimulated cAMP production of stages XIV-IV were affected by PT. Presence of the Gi-protein in both stages studied was demonstrated with PT-induced ADP ribosylation. However, no release of a putative activator of the Gi-protein could be demonstrated into spent media of the seminiferous tubules when incubated with freshly separated tubules. It is concluded that the poor FSH stimulability in cAMP production of certain spermatogenic stages of adult seminiferous tubules is at least partly due to endogenous inhibitors acting through the inhibitory Gi-protein. This inhibition could be demonstrated in a stage-dependent manner, and was present in stages with the lowest production and least stimulability of cAMP production by FSH.
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PMID:Pertussis toxin enhances follicle-stimulating hormone-stimulated cAMP production in rat seminiferous tubules in a stage-dependent manner. 254 88

We have discussed a number of agents that affect invasion and we have grouped them according to their most probable targets. This strategy is based on the following hypothesis. Invasion is the result of cellular responses to extracellular signals. Candidate signals are components of the extracellular matrix, which are rendered inactive by the flavonoid (+)-catechin (see Section III). Signals are recognized by receptors on the plasma membrane, possibly glycoproteins, that may lose their recognition function through alteration of the oligosaccharide side chains by inhibitors of protein glycosylation (see Section IV) and possibly also by alkyllysophospholipids (see Section V). Synthetic oligopeptides reflecting sequences from cell-binding domains of extracellular matrix molecules are also effective tools for blocking specific receptors (see Section VI). GTP-binding proteins (G proteins) act as signal transducers and can be inactivated by pertussis toxin (see Section VII). An intriguing aspect of both alkyllysophospholipids and pertussis toxin is that they can either inhibit the invasion of constitutively invasive cells or induce invasion of constitutively noninvasive cells. Without doubt, cellular responses implicated in invasion are many-fold. Discussed here are cell motility and directional migration with inhibition through dipyridamole and its analogs and through microtubule inhibitors, respectively (see Section VIII). Alternative hypotheses and alternative strategies for the dissection of the invasion process do exist, and alternative cellular and molecular mechanisms of action may explain the anti-invasive activity of the agents discussed earlier. The latter are mentioned in each section. It is the authors' opinion that the possibilities for exploiting the battery of anti-invasive agents have by no means been exhausted. Introducing researchers to experiments that may lead to an understanding of the mechanisms of invasion and metastasis and to new rationales for cancer treatment has been the purpose of our review.
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PMID:Anti-invasive activities of experimental chemotherapeutic agents. 268 99

In rat seminiferous epithelium, FSH-stimulated cAMP production is cyclically modulated by spermatogenic cells and is highest in stages XIV-V and lowest in stages VII-VIII of the epithelial cycle. Adenosine has been proposed to be an inhibitory paracrine molecule in Sertoli cells. In this paper the effect of adenosine analog n-phenylisopropyladenosine (PIA) on FSH-stimulated cAMP production was studied in staged rat seminiferous tubules. In low responsive stages VII-VIII of the cycle, 100 nM and 10 microM PIA inhibited FSH-stimulated cAMP production by 24% and 28%, respectively. To study whether PIA effect is mediated through Gi-protein, pertussis toxin (PT) pretreatment was used to block the Gi-protein. PT pretreatments of 3 or 18 h caused 42% or 16% elevation in FSH-stimulated cAMP production, respectively. PIA blocked the stimulation caused by PT pretreatment. At 38 days post irradiation, when spermatocytes and round spermatids were decreased in number, in stages VII-VIII of the cycle the inhibitory effect of PIA was abolished. In high responsive stages XIV-V of the cycle, 100 nM PIA stimulated cAMP production by 27%, while 10 microM PIA had no effect. At 38 days post irradiation FSH response was decreased by 19% when compared to non-irradiated level, and PIA stimulated FSH-stimulated cAMP production by 22%. The results suggest that there are stage-specific mechanisms for adenosine-dependent regulation of FSH-stimulated cAMP production in the rat seminiferous epithelium. Advanced spermatogenic cells seem to maintain the mechanisms that include PIA-mediated inhibition of FSH response. Other mechanisms than PT-sensitive Gi-protein seem to be involved in the inhibition.
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PMID:Effects of adenosine analog PIA (n-phenylisopropyladenosine) on FSH-stimulated cyclic AMP (cAMP) production in the rat seminiferous epithelium. 827 29

A phage antibody display library of single chain Fv (scFv) was derived from the peripheral blood of two patients recently recovered from pertussis infection. Ten scFv, differentiated by DNA fingerprinting, were isolated by panning the library against pertussis toxin. One scFv (type 1) accounted for 33% of clones after panning. Six of the panned scFv bound to pertussis toxin. The ability of the scFv to neutralise pertussis toxin was assessed using the Chinese hamster ovary cell assay. The predominant scFv (type 1) and two others (types IV and VIII) were able to neutralise the pertussis toxin.
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PMID:Development of neutralising human recombinant antibodies to pertussis toxin. 1022 91

Many types of cells exhibit increased adenylyl cyclase (AC) activity after chronic agonist treatment of G(i/o)-coupled receptors. This phenomenon, defined as AC superactivation or sensitization, has mostly been studied for the opioid receptors and is implicated in opiate addiction. Here we show that this phenomenon is also observed on chronic activation of the CB(1) cannabinoid receptor. Moreover, using COS-7 cells cotransfected with CB(1) receptor and individual AC isozymes, we could show selective superactivation of AC types I, III, V, VI, and VIII. The level of superactivation was dependent on the concentration of agonist and time of agonist exposure and was not dependent on the AC stimulator used. No superactivation of AC types II, IV, or VII was observed in COS-7 cells cotransfected with CB(1). The superactivation of AC type V was abolished by pretreatment with pertussis toxin and by cotransfection with the carboxy terminus of beta-adrenergic receptor kinase, which serves as a scavenger of G(betagamma) dimers, implying a role for the G(i/o) proteins and especially G(betagamma) dimers in the cannabinoid-induced superactivation of AC.
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PMID:Differential superactivation of adenylyl cyclase isozymes after chronic activation of the CB(1) cannabinoid receptor. 1072 21

We have established that treatment of cultured human skin fibroblasts with tropoelastin or with heterogenic peptides, obtained after organo-alkaline or leukocyte elastase hydrolysis of insoluble elastin, induces a high expression of pro-collagenase-1 (pro-matrix metalloproteinase-1 (pro-MMP-1)). The identical effect was achieved after stimulation with a VGVAPG synthetic peptide, reflecting the elastin-derived domain known to bind to the 67-kDa elastin-binding protein. This clearly indicated involvement of this receptor in the described phenomenon. This notion was further reinforced by the fact that elastin peptides-dependent MMP-1 up-regulation has not been demonstrated in cultures preincubated with 1 mm lactose, which causes shedding of the elastin-binding protein and with pertussis toxin, which blocks the elastin-binding protein-dependent signaling pathway involving G protein, phospholipase C, and protein kinase C. Moreover, we demonstrated that diverse peptides maintaining GXXPG sequences can also induce similar cellular effects as a "principal" VGVAPG ligand of the elastin receptor. Results of our biophysical studies suggest that this peculiar consensus sequence stabilizes a type VIII beta-turn in several similar, but not identical, peptides that maintain a sufficient conformation to be recognized by the elastin receptor. We have also established that GXXPG elastin-derived peptides, in addition to pro-MMP-1, cause up-regulation of pro-matrix metalloproteinase-3 (pro-stromelysin 1). Furthermore, we found that the presence of plasmin in the culture medium activated these MMP proenzymes, leading to a consequent degradation of collagen substrate. Our results may be, therefore, relevant to pathobiology of inflammation, in which elastin-derived peptides bearing the GXXPG conformation (created after leukocyte-dependent proteolysis) bind to the elastin receptor of local fibroblasts and trigger signals leading to expression and activation of MMP-1 and MMP-3, which in turn exacerbate local connective tissue damage.
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PMID:Conformational dependence of collagenase (matrix metalloproteinase-1) up-regulation by elastin peptides in cultured fibroblasts. 1108 20

The Ca2+-activated adenylyl cyclase type VIII (AC-VIII) has been implicated in several forms of neural plasticity, including drug addiction and learning and memory. It has not been clear whether Gi/o proteins and G-protein coupled receptors regulate the activity of AC-VIII. Here we show in intact mammalian cell system that AC-VIII is inhibited by mu-opioid receptor activation and that this inhibition is pertussis toxin sensitive. Moreover, we show that G(betagamma) subunits inhibit AC-VIII activity, while constitutively active alphai/o subunits do not. Different Gbeta isoforms varied in their efficacies, with Gbeta1gamma2 or Gbeta2gamma2 being more efficient than Gbeta3gamma2 and Gbeta4gamma2, while Gbeta5 (transfected with gamma2) had no effect. As for the Ggamma subunits, Gbeta1 inhibited AC-VIII activity in the presence of all gamma subunits tested except for gamma5 that had only a marginal activity. Moreover, cotransfection with proteins known to serve as scavengers of Gbetagamma dimers, or to reduce Gbetagamma plasma membrane anchorage, markedly attenuated the mu-opioid receptor-induced inhibition of AC-VIII. These results demonstrate that Gbetagamma (originating from agonist activation of these receptors) and probably not Galphai/o subunits are involved in the agonist inhibition of AC-VIII.
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PMID:Adenylyl cyclase type-VIII activity is regulated by G(betagamma) subunits. 1592 85

It was shown previously that chronic exposure to opiate agonists increases adenylyl cyclase (AC) activity, a phenomenon termed AC superactivation (or supersensitization). More recently, we showed that acute Gi/o- coupled receptor activation inhibits the activity of several AC isozymes, including Ca2+/calmodulin-stimulated AC-I and -VIII, whereas chronic receptor activation induces their superactivation. Here, we report that both acute Mu-opioid receptor-induced inhibition and chronic induced superactivation of AC-I and -VIII are pertussis toxin sensitive. In addition, we show that proteins that interfere with the activity of Gbetagamma subunits (Gbetagamma scavengers) strongly attenuate the acute inhibition of AC-I and -VIII and the superactivation of AC-I, and abolish the superactivation of AC-VIII. Based on these results, we suggest that Gbetagamma is involved in the acute inhibition and chronic agonist-induced superactivation of AC types I and VIII.
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PMID:Inhibition and superactivation of the calcium-stimulated isoforms of adenylyl cyclase: role of Gbetagamma dimers. 1618 30

Acute and chronic activation of opioid receptors differentially regulate the activity of the various adenylyl cyclase (AC) isoforms. In several AC isoforms (I, V, VI and VIII) acute opioid activation (by agonists such as morphine) leads to AC inhibition, while prolonged opioid activation leads to increase in AC activity, a phenomenon known as AC sensitization or superactivation. In several other AC isoforms (II, IV and VII), acute opioid activation leads to AC stimulation, while chronic opioid exposure inhibits AC activity, in a process, which in analogy to the term "superactivation" is referred to as "superinhibition". AC-II is highly regulated by multiple and independent biochemical stimuli, including Gbetagamma, Galphas and PKC activation. We investigated the regulation of AC-II by Galphas and by PKC under conditions of acute and chronic exposure to opioid agonists in COS-7 transfected cells. We found that acute opioid exposure led to an increase in AC-II activity by either Galphas or PKC stimulation. This effect seems to be regulated by Gbetagamma subunits, in both activation pathways, as the increase in AC-II activity was abolished by pertussis toxin treatment and by Gbetagamma scavengers. On the other hand, while chronic opioid exposure led to a decrease in AC-II activity ("superinhibition") upon stimulation of the Galphas pathway, this superinhibition was not observed when the opioid treated cells were stimulated via PKC activation.
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PMID:Adenylyl cyclase type II activity is regulated by two different mechanisms: implications for acute and chronic opioid exposure. 1654 1


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