Pertussis is an acute respiratory disease caused by the bacterium Bordetella pertussis, for which humans are the only known reservoir. During infection, B. pertussis releases several toxins, including pertussis toxin (PT) and adenylate cyclase toxin (ACT), which have both been shown to play roles in promoting bacterial growth during early infection in a mouse model. Furthermore, in vitro and in...

The relationship between the structure of the A subunit of pertussis toxin and its function was analyzed. Limited tryptic digestion of the A subunit converted the protein to two stable fragments (M. = 20,000 and 18,000). Antibodies raised to synthetic peptides homologous to regions in the A subunit were used to map these fragments. Both fragments were shown to contain the NHz-terminal portion b...

Three murine monoclonal antibodies (MAb), E19, E205, and E251, raised against pertussis toxin reacted in Western blots (immunoblots) with the S1, S4, and S2-S3 subunits, respectively, and neutralized the Chinese hamster ovary cell-clustering activity of pertussis toxin. MAb E251 recognized a linear synthetic peptide corresponding to amino acids 107 to 120 of the S2 subunit, suggesting a role fo...

The formation of vesicles for protein trafficking requires the dynamic binding of cytosolic coat proteins onto Golgi membranes and this binding is regulated by a variety of GTPases, including heterotrimeric G proteins. We have previously shown the presence of the pertussis toxin-sensitive G alpha i-3 protein on Golgi membranes and demonstrated a functional role for G alpha i-3 in the traffickin...

The pathogenesis of the myopathy occurring in the heart of the cardiomyopathic strain of the Syrian hamster is not well understood but is believed to be associated with abnormal calcium handling by myopathic cells. The purpose of this study was to determine whether the cardiomyopathy occurring in strain BIO 14.6 animals is associated with an enhanced a1-adrenergic receptor-mediated rise in cyto...

There is evidence that pertussis is reemerging in vaccinated populations. We have proposed, and provided evidence for, one explanation for this phenomenon in The Netherlands: antigenic divergence between vaccine strains and circulating strains. Finland has a pertussis vaccination history very similar to that of The Netherlands, and yet there is no evidence for an increase in the incidence of pe...

The binding of the chemotactic peptide N-formyl-methionyl-leucyl-phenylalanine to its cell surface receptor rapidly elicits the hydrolysis of phosphatidylinositol 4,5-bisphosphate by phospholipase C to form the putative second messengers inositol 1,4,5-trisphosphate and sn-1,2-diacylglycerol. To investigate the possible role of a guanine nucleotide binding protein in transduction of this membra...

The effect of proadrenomedullin NH2-terminal 20 peptide (PAMP) on the voltage-gated Ca2+ channel current was investigated using the perforated whole-cell clamp technique on NGF-treated PC12 cells. PAMP inhibited the Ba2+ current through N-type Ca2+ channels in a concentration dependent manner. Injection of GDPbetaS into the cell abolished the inhibition while injection of GTPgammaS into the cel...