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

The modulating effects of pertussis toxin on angiotensin II and B-HT 920-evoked hemodynamic changes were compared with those of milrinone to evaluate the possible role of guanine nucleotide regulatory proteins (G proteins) in the mechanism of action of milrinone. Both milrinone and pertussis toxin shifted the blood pressure dose-response curves of B-HT 920 to the right, but the responses to angiotensin II were decreased after milrinone pretreatment only. The increase in cardiac frequency evoked by milrinone and isobutylmethylxanthine (IBMX) was not sensitive to pertussis toxin. In contrast, the decrease in systolic blood pressure elicited by milrinone could be prevented by pertussis toxin pretreatment, suggesting the involvement of a regulatory protein. Milrinone and IBMX did not influence the effects of arecoline on blood pressure or heart rate in either normal or pertussis toxin-pretreated rats. It is concluded that milrinone may affect a G protein, but not the adenylate cyclase-associated inhibitory protein, Gi.
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PMID:Cardiovascular responses to milrinone in pertussis toxin-pretreated pithed rats. 170 16

Cholinergic inhibition of atrial contraction is typically followed by a rebound positive inotropic response. In the present study, we used a nystatin-perforated patch whole-cell recording method to determine whether acetylcholine (ACh) elicits a rebound stimulation of L-type Ca2+ current (ICa,L) in cat atrial myocytes. ACh (1 mumol/L) decreased basal ICa,L (-19 +/- 2%). Within approximately 30 s of returning to ACh-free solution, basal ICa,L exhibited a rebound increase above the control level (+61 +/- 7%) that returned to the control level within 4 to 5 minutes. ACh elicited concomitant changes in cell shortening, ie, a decrease followed by a rebound increase. The EC50 and maximal response of ACh-induced inhibition and rebound stimulation of ICa,L were 1.9 x 10(-9) mol/L and -30%, respectively, and 2.9 x 10(-8) mol/L and +64%, respectively. All effects of ACh on ICa,L were blocked by prior exposure to 1 mumol/L atropine or 100 mumol/L AFDX116 and unaffected by 0.2 mumol/L pirenzepine or 1 mumol/L propranolol. In the presence of ACh, exposure to atropine elicited stimulation of ICa,L.ACh-induced inhibition and rebound stimulation of current were independent of external Ca2+. Rebound stimulation of ICa,L was associated with a negative shift in the voltage dependence of ICa,L activation. Inhibition of protein kinase A by 50 mumol/L Rp-cAMPs decreased basal ICa,L by 36 +/- 1% and abolished the rebound stimulation of ICa,L. Forskolin (0.01 mumol/L) or isoproterenol (0.01 mumol/L) had no effect on basal ICa,L, but each accentuated the rebound increase in ICa,L. When adenylate cyclase was maximally stimulated with 1 mumol/L isoproterenol plus 2 mumol/L forskolin, ACh decreased ICa,L but failed to elicit rebound stimulation of ICa,L. Milrinone (10 mumol/L) increased basal ICa,L by 70 +/- 7% and significantly attenuated the rebound stimulation of ICa,L. Exposure to 1 mmol/L 8-bromo-cGMP elicited a small decrease in basal ICa,L, attenuated ACh-induced inhibition, and enhanced the rebound stimulation of ICa,L. Incubation in pertussis toxin prevented all ACh-induced changes in ICa,L. Inhibition of nitric oxide synthase by 100 mumol/L NG-monomethyl-L-arginine (L-NMMA) decreased basal ICa,L by -20 +/- 5%, prevented ACh-induced inhibition, and markedly attenuated the rebound stimulation of ICa,L. We conclude that in cat atrial myocytes ACh acts via M2 muscarinic receptors and pertussis toxin-sensitive G protein to inhibit basal ICa,L and that on withdrawal ACh elicits a rebound stimulation of ICa,L. Rebound stimulation of ICa,L is mediated via cAMP-dependent protein kinase A enhanced by ACh-induced inhibition of phosphodiesterase.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Acetylcholine elicits a rebound stimulation of Ca2+ current mediated by pertussis toxin-sensitive G protein and cAMP-dependent protein kinase A in atrial myocytes. 789 37