Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0043167 (pertussis)
 19,595 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

More than two isoforms have been identified for angiotensin receptors based on their ligand selectivity. The objective of this study is to determine the molecular structure of angiotensin type 2 receptor (AT2), whose physiological functions are still an enigma despite extensive studies on its distribution in fetal tissues. We expression-cloned a cDNA of an affinity-purified AT2 from rat pheochromocytoma cells (PC12w). The AT2 cDNA clone comprises 2,868 nucleotides and encodes a 363 amino acid protein with seven putative transmembrane domains. The dissociation constant for its binding to 125I-CGP42112A, an AT2-specific ligand, was 0.11 +/- 0.01 nM. Its binding to 0.5 nM 125I-[Sar1,Ile8]-Ang II was not inhibited by Dup 753 but by PD123319 (IC50 = 1.7 +/- 0.2 nM). These binding features are characteristic of angiotensin type 2 receptor. The amino acid sequence analysis of the purified AT2 corroborated the amino terminus of the deduced primary structure of AT2. Angiotensin type 1 receptor (AT1) is the most closely related to AT2 but with only 32% amino acid sequence identity. Angiotensin II attenuated membrane-associated protein tyrosine phosphatase activity in the COS-7 cells stably expressing AT2 through a pertussis toxin-sensitive G protein. However, the physiological function of AT2 in the fetal kidney is still unresolved.
 ...
PMID:Molecular structure and function of angiotensin type 2 receptor. 769 90

A primary cellular site involved in heat shock response of eukaryotic cells is located in plasma membranes. The mechanism by which heat shock is sensed and the signals that trigger heat shock response remain an enigma. We aim to determine the role of guanine-nucleotide binding proteins (G)-proteins in mediating heat shock response in eukaryotic cells. The effect of heat shock on high affinity GTPase activity in presence or absence of modulators of G-proteins, such as pertussis toxin was studied by measuring GTPase catalyzed release of 32[Pi] from gamma-32[P]GTP. The effect of pertussis toxin on induction of heat shock proteins in cells subjected to thermal stress was studied by SDS-PAGE analysis of 35[S]-methionine labelled cellular proteins. Exposure of cultured human malignant cells to thermal stress (43 degrees C) resulted in a significant increase in activity of high affinity GTPase in the membranes (P < 0.001). This response to heat shock was inhibited by prior exposure of the cells to nanogram concentrations of pertussis toxin, suggesting the involvement of G-proteins in mediating heat shock response. To characterize this G-protein dependence further, we assayed thermal stress stimulated high affinity GTPase activity in cells pretreated with antisera (AS/7) raised against a synthetic peptide corresponding to the last 10 amino acids of alpha-subunit of inhibitory G-protein (Gi). A partial reduction in heat shock induced stimulation of GTPase activity was observed in the presence of this antisera. The pertussis toxin treated cells did not show induction of heat shock proteins in response to thermal stress.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Heat stress stimulates high affinity GTPase in cervical carcinoma cells. 778 Aug 30

The role of M2 and M3 receptors in the contractile and phosphoinositide responses elicited to oxotremorine-M was investigated in the guinea pig colon. Under standard conditions, both the contractile and phosphoinositide responses were insensitive to pertussis toxin and irreversibly antagonized by alkylation of M3 receptors with N-(2-chloroethyl)-4-piperidinyl diphenylacetate. After treatment with N-(2-chloroethyl)-4-piperidinyl diphenylacetate, the remaining contractile response was sensitive to pertussis toxin and weakly antagonized by the M2- and M4-selective antagonist AF-DX 116. In contrast, the residual phosphoinositide response was unaffected by pertussis toxin. The pertussis toxin sensitivity of the remaining contractile response suggests that the M2 receptor is mediating the contraction, whereas its weak antagonism by AF-DX 116 suggests that an alternate muscarinic subtype mediates the response. To explain this enigma, we investigated a mathematical model for receptor action based on an interaction between two receptor subtypes (M2 and M3). This model predicts that a response mediated by both the M2 and M3 receptor can be pertussis toxin sensitive yet exhibit an antagonistic profile indicative of an M3 response.
 ...
PMID:Muscarinic M3 receptor inactivation reveals a pertussis toxin-sensitive contractile response in the guinea pig colon: evidence for M2/M3 receptor interactions. 1008 39

Understanding the biological mechanisms underlying episodic outbreaks of infectious diseases is one of mathematical epidemiology's major goals. Historic records are an invaluable source of information in this enterprise. Pertussis (whooping cough) is a re-emerging infection whose intermittent bouts of large multiannual epidemics interspersed between periods of smaller-amplitude cycles remain an enigma. It has been suggested that recent increases in pertussis incidence and shifts in the age-distribution of cases may be due to diminished natural immune boosting. Here we show that a model that incorporates this mechanism can account for a unique set of pre-vaccine-era data from Copenhagen. Under this model, immune boosting induces transient bursts of large amplitude outbreaks. In the face of mass vaccination, the boosting model predicts larger and more frequent outbreaks than do models with permanent or passively-waning immunity. Our results emphasize the importance of understanding the mechanisms responsible for maintaining immune memory for pertussis epidemiology.
...
PMID:Immune boosting explains regime-shifts in prevaccine-era pertussis dynamics. 2399 Oct 47