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Query: UMLS:C0043167 (pertussis)
 19,595 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of pertussis toxin, forskolin and phosphodiesterase inhibitors on the antinociceptive action of intrathecal purines were examined to investigate the possible involvement of adenylate cyclase in spinal antinociception. Pretreatment with pertussis toxin (0.25 and 0.5 microgram) inhibited the antinociceptive action of L-phenyl-isopropyladenosine (L-PIA), N6-cyclohexyladenosine (CHA) and 5'-N-ethylcarboxamide adenosine (NECA) in the tail flick and hot plate tests. Forskolin (10-30 micrograms) reduced the effect of CHA and NECA in the hot plate test. Ro 201724 (30 micrograms) and Rolipram (20 micrograms) inhibited CHA in the tail flick and hot plate tests, but did not affect NECA in either test. These results suggest (1) spinal antinociception by purines is mediated by interactions with G-proteins (Gi linked to adenylate cyclase and/or Go linked to ion channels) (2) spinal antinociception by CHA is due to inhibition of adenylate cyclase (3) a separate mechanism, which does not involve stimulation of adenylate cyclase, may be involved in the spinal action of NECA.
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PMID:Role of G-proteins and adenylate cyclase in antinociception produced by intrathecal purines. 314 8

We studied the effect of several compounds that influence different cell activation steps on platelet-activating factor (PAF)-induced basophil histamine secretion. Isobutylmethylxanthine (1-100 microM), dimaprit (1-100 microM) and dibutyryl adenosine 3',5'-cyclic phosphate (cAMP; 0.01-1 mM), that increase intracellular cAMP levels, concentration-dependently inhibited PAF-elicited histamine release. Rolipram (phosphodiesterase, PDE, isotype IV inhibitor; 0.1 nM-10 microM) potently inhibited histamine secretion activated by PAF, whereas SKF95654 (PDE III inhibitor; 0.01-10 microM) was ineffective. The kinase inhibitor, staurosporine (0.1-100 nM), enhanced PAF-induced basophil histamine release, whereas the G-protein inhibitor, pertussis toxin (1 microgram/ml), had an inhibitory effect. The specific lipoxygenase inhibitor, AA-861 (0.1-10 microM), inhibited PAF-activated histamine release, while the leukotriene A4 hydrolase inhibitor, bestatin (100 microM), had only a marginal effect. Finally, the Ca2+ channel entry blockers, verapamil (3-30 microM) and zinc (1.5-50 microM), inhibited PAF-induced histamine release. These results suggest that PAF is a unique secretagogue for human basophils unlike antigen, anti-IgE or univalent stimuli.
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PMID:Pharmacologic control of histamine release from human basophils induced by platelet-activating factor. 769 3

Phosphorylation of the beta(2) adrenoreceptor (beta(2)AR) by cAMP-activated protein kinase A (PKA) switches its predominant coupling from stimulatory guanine nucleotide regulatory protein (G(s)) to inhibitory guanine nucleotide regulatory protein (G(i)). beta-Arrestins recruit the cAMP-degrading PDE4 phosphodiesterases to the beta(2)AR, thus controlling PKA activity at the membrane. Here we investigate a role for PDE4 recruitment in regulating G protein switching by the beta(2)AR. In human embryonic kidney 293 cells overexpressing a recombinant beta(2)AR, stimulation with isoprenaline recruits beta-arrestins 1 and 2 as well as both PDE4D3 and PDE4D5 to the receptor and stimulates receptor phosphorylation by PKA. The PKA phosphorylation status of the beta(2)AR is enhanced markedly when cells are treated with the selective PDE4-inhibitor rolipram or when they are transfected with a catalytically inactive PDE4D mutant (PDE4D5-D556A) that competitively inhibits isoprenaline-stimulated recruitment of native PDE4 to the beta(2)AR. Rolipram and PDE4D5-D556A also enhance beta(2)AR-mediated activation of extracellular signal-regulated kinases ERK12. This is consistent with a switch in coupling of the receptor from G(s) to G(i), because the ERK12 activation is sensitive to both inhibitors of PKA (H89) and G(i) (pertussis toxin). In cardiac myocytes, the beta(2)AR also switches from G(s) to G(i) coupling. Treating primary cardiac myocytes with isoprenaline induces recruitment of PDE4D3 and PDE4D5 to membranes and activates ERK12. Rolipram robustly enhances this activation in a manner sensitive to both pertussis toxin and H89. Adenovirus-mediated expression of PDE4D5-D556A also potentiates ERK12 activation. Thus, receptor-stimulated beta-arrestin-mediated recruitment of PDE4 plays a central role in the regulation of G protein switching by the beta(2)AR in a physiological system, the cardiac myocyte.
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PMID:beta-Arrestin-mediated PDE4 cAMP phosphodiesterase recruitment regulates beta-adrenoceptor switching from Gs to Gi. 1255 97

The removal by phagocytosis of degenerated myelin is central for repair in Wallerian degeneration that follows traumatic injury to axons and in autoimmune demyelinating diseases (e.g., multiple sclerosis). We tested for roles played by the cAMP cascade in the regulation of myelin phagocytosis mediated by complement receptor-3 (CR3/MAC-1) and scavenger receptor-AI/II (SRAI/II) separately and combined in mouse microglia and macrophages. Components of the cAMP cascade tested are cAMP, adenylyl cyclase (AC), Gi, protein kinase A (PKA), exchange protein directly activated by cAMP (Epac), and phosphodiesterases (PDE). PKA inhibitors H-89 and PKI(14-22) amide inhibited phagocytosis at normal operating cAMP levels (i.e., those occurring in the absence of reagents that alter cAMP levels), suggesting activation of phagocytosis through PKA at normal cAMP levels. Phagocytosis was inhibited by reagents that elevate endogenous cAMP levels to above normal: Gi-inhibitor Pertussis toxin (PTX), AC activator Forskolin, and PDE inhibitors IBMX and Rolipram. Phagocytosis was inhibited also by cAMP analogues whose addition mimics abnormal elevations in endogenous cAMP levels: nonselective 8-bromo-cAMP, PKA-specific 6-Benz-cAMP, and Epac-specific 8-CPT-2'-O-Me-cAMP, suggesting that abnormal high cAMP levels inhibit phagocytosis through PKA and Epac. Altogether, observations suggest a dual role for cAMP and PKA in phagocytosis: activation at normal cAMP levels and inhibition at higher. Furthermore, a balance between Gi-controlled cAMP production by AC and cAMP degradation by PDE maintains normal operating cAMP levels that enable efficient phagocytosis.
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PMID:cAMP cascade (PKA, Epac, adenylyl cyclase, Gi, and phosphodiesterases) regulates myelin phagocytosis mediated by complement receptor-3 and scavenger receptor-AI/II in microglia and macrophages. 1634 30