Pertussis Mitogenicity

Functionally, the Dl-like receptors (Dl, D5) are coupled to the G protein Gas and thus can stimulate adenylyl cyclase. The D2-like receptors (D2, D3, and D4) couple to pertussis toxin sensitive G proteins (Gai/0), and consequently inhibit adenylyl cyclase activity. While the Dl-like receptors almost exclusively signal through Gas-mediated activation of adenylyl cyclase, the D2-like receptors have been reported to modulate the activity of a plethora of signaling molecules and pathways. Many of these actions are mediated through the G(3y subunit. Some of these molecules and pathways include the calcium channels, potassium channels, sodium-hydrogen exchanger, arachidonic acid release, and mitogen-activated protein kinase pathways. 

The OP group of receptois share common effector mechanisms. All receptois couple via pertussis toxin-sensitive Go and Gi proteins leading to (i) inhibition of adenylate cyclase (ii) reduction of Ca2+ currents via diverse Ca2+ channels (hi) activation of inward rectifying K+ channels. In addition, the majority of these receptors cause the activation of phospholipase A2 (PLA2), phospholipase C 3 (PLC 3), phospholipase D2 and of MAP (mitogen-activated protein) kinase (Table 3). 

Del Como M, Liu QH, Schols D, et al. HIV-1 gpl20 and chemokine activation of Pyk2 and mitogen-activated protein kinases in primary macrophages mediated by calcium-dependent, pertussis toxin-insensitive chemokine receptor signaling. Blood 2001 98(10) 2909—2916. 

Pertussis toxin has a high mitogenic potential. This can be avoided by heat inactivation for 20 min in an 80°C water bath. 

The 5-HT1A receptor is a member of the 5-HT] family of serotonin receptors best known for their capacity to inhibit adenylyl cyclase activity via pertussis toxin-sensitive G proteins. These receptors also couple to K+ channels, Ca2+ channels, PLC, intracellular calcium, mitogen-activated protein kinase cascade, and Na+/K+-ATPase (73,74). This receptor is an important target for the management of anxiety, depression, and schizophrenia (75-78). 

Lobet Y, Feron C, Dequesne G, et al. (1993) Site-specific alterations in the B-oligomer that affect receptor-binding activities and mitogenicity of pertussis toxin. In J. Exp. Med. 177 79—87. 

Mercaptopyrldoxine (62) was reported to enhance the intensity of the secondary reaction in adjuvant arthritic rats and to augment pertussis vaccine edema. Also, it stimulated lymphocyte responses to Concanavalin A.203 Another sulfhydryl compound, a-mercaptoproplonylglyclne (64), enhanced antibody formation to SRBC in mice when given for five days before immunization. T- and B-cell mitogen reactivity of lymphoid cells from EL4 leukemia-bearing mice was restored and production of cytotoxic antibody to EL4 increased by the administration of 64.204... 

Higher micromolar concentrations of RANTES have been reported to be mitogenic for T lymphocytes, and to induce lymphokine production and the expression of IL-2Ra (Bacon et al., 1995). This T cell response is herbimycin A- rather than pertussis toxin-sensitive, suggesting the involvement of non-Gi coupled STM receptor-dependent signal transduction by tyrosine kinases (Bacon et al., 1995). The physiological relevance of this observation remains to be established. 

PTX, pertussis toxin PLC, phospholipase C PTP, phosphotyrosine phosphatase AC, adenyl cyclase MAP, mitogen-activated protein (kinase). 

Morse JH, Kong AS, Lindenbaum J et al. Ihe mitogenic effect of the lymphocytosis promoting fictor from Bordetella pertussis on human lymphocytes. J Clin Invest 1977 60(3) 683-692. 

---