Pertussis Translocation

Excitation of smooth muscle via alpha-1 receptors (eg, in the utems, vascular smooth muscle) is accompanied by an increase in intraceUular-free calcium, possibly by stimulation of phosphoUpase C which accelerates the breakdown of polyphosphoinositides to form the second messengers inositol triphosphate (IP3) and diacylglycerol (DAG). IP3 releases intracellular calcium, and DAG, by activation of protein kinase C, may also contribute to signal transduction. In addition, it is also thought that alpha-1 adrenergic receptors may be coupled to another second messenger, a pertussis toxin-sensitive G-protein that mediates the translocation of extracellular calcium. 

A nasopharyngeal swab obtained from a 4-month-old infrint with rhinitis and paroxysmal coughing tested positive upon culture for Bordetella pertussis. He was admitted to the hospital for therapy with an antibiotic that inhibits the translocation of peptidyl-tRNA on 70S ribosomes, This patient was most likely treated with... 

Answer A. Erythromycin is the antibiotic of choice for pertussis. It inhibits translocation. 

C. botulinum toxins belong to the AB group of toxins, which also includes diphtheria toxin, pseudomonas exotoxin A, anthrax toxin, Shiga(like) toxin, cholera toxin, pertussis toxin, and plant toxins, e.g., ricin. Moiety A has an enzymatic activity and usually modified cellular-target entering cytosol. Moiety B consists of one or more components and binds the toxin to surface receptors, and is responsible for translocation of the A component into cells. AB toxins are produced in a non-active form and are activated by a split between two cysteine residues within a region (Falnes and Sandvig, 2000). 

This reaction is reversible when conducted in vitro, but under the conditions of pH and nicotinamide concentration that exist in the cell, it is irreversible. Thus, diphtheria toxin kills cells by irreversibly destroying the ability of EF-2 to participate in the translocation step of protein synthesis elongation. A number of other protein toxins have subsequently been found to ADP-ribosylate and inactivate cellular proteins involved in other essential cellular pathways. For example, cholera and pertussis toxins ADP-ribosylate and inactivate proteins important to cAMP metabolism. 

To further address the signaling pathways involved in opioid-induced cardioprotection, Schultz et al. [55] determined the involvement of a Gi/o protein in mediating delta -induced cardioprotection produced by the selective nonpeptide delta opioid agonist, TAN-67. Pretreatment with pertussis toxin for 48 h prior to TAN-67 administration completely blocked its cardioprotective elfect as well as that to IPC, suggesting that a Gi/o protein is intimately involved in the cardioprotection produced by these two interventions. Subsequently, Miki et al. [56] found that morphine produced a cardioprotective elfect in isolated rabbit hearts which was blocked by pretreatment with chelerythrine, a protein kinase C (PKC) inhibitor at a concentration that had no elfect on infarct size in the absence of morphine. More recently, Fryer et al. [57] extended these findings to the intact rat heart and showed that the protective elfect of TAN-67 to reduce infarct size was blocked by chelerythrine and GF 109203X, two selective PKC inhibitors with different binding sites, and that TAN-67 produced a selective translocation of the PKC-delta isoform to the mitochondria. 

Pertussis toxin consists of two components, the enzymatically active A protomer consisting of a single polypeptide, and the penta-meric B oligomer (Tamura et ai, 1982). The B component is involved in binding to the surface of eukaryotic target cells, and presumably in translocation of the toxin across the plasma membrane. Once inside the cell, the enzymatically active A component needs to undergo activation that depends on reduced gluthathione this effect can be... 

PIP3, and thus their functions are thought to be regulated by PI3K activity [437], The Tec family members Tec, Bmx, and Btk have been identified in neutrophils. N-formyl peptide-induced phosphorylation and translocation of these proteins from the cytosol to membrane fractions are sensitive to pertussis toxin and PI3K inhibitors [194], A possible role of these kinases in migration remain to be explored. 

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