alpha-Adrenergic inhibition of the beta-adrenoceptor-dependent chloride current in guinea-pig ventricular myocytes.
1. alpha 1-Adrenoceptor-mediated inhibition of the beta-adrenoceptor-dependent Cl- current was investigated in guinea-pig ventricular myocytes using the patch clamp technique. The Cl- conductance activated by noradrenaline (0.1-10 microM) with an alpha 1-blocker (prazosin, 5 microM) was significantly greater than that activated by noradrenaline alone. Phenylephrine and methoxamine, alpha 1-agonists, exerted an inhibitory effect on the Cl- conductance activated by isoprenaline. The dose-response relationship for isoprenaline and the Cl- current activation was shifted to higher doses in the presence of phenylephrine (30 microM). 2. The interaction of alpha 1- and beta-agonists on Cl- current was also observed on the single channel level; in some of the outside-out membrane patches, phenylephrine (50 microM) depressed the activity of the single Cl- channel which was induced by 5 microM adrenaline. 3. Phenylephrine had no effect on the Cl- conductance induced by forskolin (0.5-5 microM), an activator of adenylate cyclase. The Cl- conductance activated persistently by isoprenaline in GTP gamma S-loaded cells was also insensitive to phenylephrine. The results suggest that the observed alpha 1-adrenergic attenuation of the beta-adrenergic response is not primarily due to inhibition of adenylate cyclase activity. The alpha 1-adrenergic action may interfere with the processes leading to enzyme activation in the beta-adrenergic pathway.
Iyadomi
I
I
Department of Physiology, Saga Medical School, Japan.
Hirahara
K
K
Ehara
T
T
D000818:Animals; D018118:Chloride Channels / Q000187:drug effects / Q000502:physiology*; D005576:Colforsin / Q000494:pharmacology; D004837:Epinephrine / Q000494:pharmacology; D006168:Guinea Pigs; D006352:Heart Ventricles / Q000187:drug effects; D018408:Patch-Clamp Techniques; D011224:Prazosin / Q000494:pharmacology; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000502:physiology*; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000502:physiology*; D016276:Ventricular Function
D018118:Chloride Channels; D011942:Receptors, Adrenergic, alpha; D011943:Receptors, Adrenergic, beta; D005576:Colforsin; D011224:Prazosin; D004837:Epinephrine