Pertussis toxin-sensitive and -insensitive mechanisms of alpha1-adrenoceptor-mediated inotropic responses in rat heart.
In rat left ventricular papillary muscle, phenylephrine, an alpha1-adrenoceptor agonist, induced a triphasic inotropic response; an initial transient, small, positive inotropic effect followed by a transient chloroethylclonidine-sensitive negative inotropic effect and a sustained 2-(2,6-dimethoxyphenoxyethyl)aminomethyl-1,4-benzodioxane (WB4101)-sensitive positive inotropic effect. Treatment with pertussis toxin for 2 days significantly inhibited only the transient negative inotropic effect without changing the sustained positive inotropic effect. This treatment also prevented the acetylcholine (1 microM)-induced negative inotropic effect. Further, phenylephrine-induced transient negative inotropic effect was attenuated in the presence of ouabain. These results suggest that pertussis toxin-sensitive or -insensitive G-protein may be responsible for alpha1-adrenoceptor subtype-mediated negative inotropic effect or positive inotropic effect, respectively, in which the transient negative inotropic effect was produced via the stimulation of Na+, K+ pump, presumably through pertussis toxin-sensitive G-protein-dependent pathway.
Otani
H
H
Department of Pharmacology, Kansai Medical University, Moriguchi City, Osaka, Japan. otani@takii.kmu.ac.jp
Oshiro
A
A
Yagi
M
M
Inagaki
C
C
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D003000:Clonidine / Q000031:analogs & derivatives / Q000494:pharmacology; D004347:Drug Interactions; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D037342:Pertussis Toxin; D010656:Phenylephrine / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects*; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology; D010566:Virulence Factors, Bordetella / Q000494:pharmacology*
D000317:Adrenergic alpha-Antagonists; D011942:Receptors, Adrenergic, alpha; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D010566:Virulence Factors, Bordetella; D010656:Phenylephrine; C051731:chlorethylclonidine; D011433:Propranolol; D037342:Pertussis Toxin; D003000:Clonidine