Pertussis Secretion

Cockcroft, S., Stutchfield, J. (1989). ATP stimulates secretion in human neutrophils and HL60 cells via a pertussis toxin-sensitive guanine nucleotide-binding protein coupled to phospholipase C. FEBS Lett. 245,25-9. 

The G-protein that has been termed Gp, and that is linked to phospholipase C activation, may in fact be Gaj 2 or Gc. 3. Ga is designated as the G-protein responsible for activation of phospholipase A2, which results in arachidonic acid release. Some experimental evidence indicates that, at least in HL-60 cells, different agonists can preferentially activate different phospholipases, and some of these are responsible for the activation of secretion. In neutrophils, the two pertussis-toxin-sensitive Ga-proteins (Gaj-2 and G j 3) have been identified by peptide mapping of proteolytic digests of the proteins, by peptide sequencing and by immunoblotting. Complementary-DNA clones for the mRNA of these two molecules have also been isolated from an HL-60 cDNA library. Gai-2 is five to ten times more abundant than Gai.3, the former component comprising 3% of the total plasma membrane proteins. It is possible that these two different Ga-subunits are coupled to different phospholipases (e.g. phospholipases C and D). Pertussis toxin inhibits the secretion of O2 after stimulation of neutrophils by fMet-Leu-Phe, but pertussis-toxin-insensitive G-proteins are also present in neutrophils. These may be members of the Gq family and may be involved in the activation of phospholipase Cp (see 6.3.1). 

Pertussis toxin is a protein secreted by the bacterium Bordetella pertussis which causes whooping cough. The toxin enters a cell where it also catalyses ADP-ribosylation of the a-subunit of G-protein. 

Aniseed is stated to possess expectorant, antispasmodic, carminative, and parasiticidic properties. It is traditionally used for bronchial catarrh, pertussis, spasmodic cough, flatulent colic, topically for pediculosis and scabies, and specifically for bronchitis, tracheitis with persistent cough, and as an aromatic adjuvant to prevent colic from cathartics. It has been used as an estrogenic agent and is reputed to increase milk secretion, promote menstruation, facilitate birth, alleviate symptoms of the male climacteric, and increase libido. 

Meller E, Puza T, Diamond J, Lieu HD, Bohmaker K. Comparative effects of receptor inactivation, 17 beta-estradiol and pertussis toxin on dopaminergic inhibition of prolactin secretion in vitro. J Pharmacol Exp Ther 1992 263 462-469. 

Histamine receptors variously mediate the bronchoconstrictant, inflammatory, irritant, vasodilator, gastric pepsin secretion and immune suppression actions of histamine. Associated with the immune response, cytokines cause release of histamine from mast cells. Histamine acts via HI, H2, H3 and H4 GPCRs. HI and H2 receptors couple via both Gas (elevating cAMP) and Gaq (elevating Ca2+ in a pertussis toxin-insensitive fashion) and H3 couples via Gai (decreasing cAMP). 

Johnson FD, Bums DL (1994) Detection and subcellular localization of three PtI proteins involved in the secretion of pertussis toxin from Bordetella pertussis. In J. Bacterial. 176 5350-5356. 

Kotob SI, Hausman SZ, Burns DL (1995) Localization of the promoter for the ptI genes in Bordetella pertussis, which encode proteins essential for secretion of pertussis toxin. In Infect. Immun. 63 3227-3230. 

Weiss AA, Johnson FD, Burns DL (1993) Molecular characterization of an operon required for pertussis toxin secretion. In Proc. Natl. Acad. Sci. USA 90 2970-2974. 

Schmidt A, Hescheler J, Offermanns S et al. (1991) Involvement of pertussis toxin-sensitive currents in an insulin-secreting cell line (RINmSF). In J. Biol. Chem. 266 18025-18033... 

The mechanism by which epinephrine and other neurohormones inhibit insulin secretion involves pertussis toxin-sensitive G-proteins. These hormones exert multiple actions, all contributing to the marked reduction of stimulated insulin secretion (Ullrich and Wollheim, 1988, Lang ef al., 1993). They thus inhibit adenylyl cyclase activity, hyperpo-larize the membrane potential by increasing K conductance, and... 

Donovan MG, Storm DR (1990) Evidence that the adenylate cyclase secreted from Bordetella pertussis does not enter animal cells by receptor-mediated endocyto-sis. J Cell Physiol 145 444-449. 

The treated toxins are sometimes referred to as formol toxoids. Toxoid vaccines are very effective in the prevention of those diseases such as diphtheria, tetanus, botulism and clostridial infections of farm animals, in which the infecting bacteria produce disease through the toxic effects of secreted proteins which enzymically modify essential cellular components. Many of the clostridial toxins are lytic enzymes. Detoxification is also required for the pertussis toxin component of acellular pertussis vaccines. 

Bronchiectasis is the irreversible dilation of parts of the bronchi that results in the formation of pockets where secretions can accumulate. These pockets create an environment that fosters the growth of bacteria and infection. Bacteria commonly found in bronchiectasis are Staphylococcus, Klebsiella, and Bordetella pertussis. These are treated with antibiotics (see chapter 13). 

O Callaghan, D., Cazevieille, C., Allardet-Serven, A., Boschiroli, M.L., Bourg, G., Foulongne, V., Frutos, P., Kulakov, Y., Ramuz, M. 1999. A homologue of the Agrobacterium tumefaciens VirB and Bordetella pertussis Ptl type IV secretion systems is essential for intracellular survival of Brucella suis. Mol. Microbiol. 33 1210-1220. 

Cholera and pertussis toxins catalyze the covalent addition of ADP-ribose to specific sites in the ot subunits of Gs and Gi, respectively. This modification inhibits GTPase action in the ot subunits and converts them to irreversible activators of adenylate cyclase. As a result, cAMP accumulates. In the intestine, the response to this is an uncontrollable secretion of water and sodium—causing severe diarrhea and dehydration. 

Insulin-releasing peptide (RK-13), RRKPLF-PFipiORPK, an insulinotropic 13-peptide isolated from the skin secretion of Agalych-nis calcarifer frogs. It shows sequence identity in seven of the 13 amino acid residues to the N-terminal sequence of PR-39. Synthetic RK-13 stimulated insulin release in a dose-dependent, glucose-sensitive manner, exerting its effects via a cAMP-protein kinase A pathway, independent of pertussis toxin-sensitive G proteins [Y. H. A. Abdel-Wahab et al., Biol. Chem. 2005, 386, 581]. 

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