Mitogenicity, Pertussis toxin

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. 

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). 

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