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alpha‐Adrenergic inhibition of the beta‐adrenoceptor‐dependent chloride current in guinea‐pig ventricular myocytes.
Author(s) -
Iyadomi I,
Hirahara K,
Ehara T
Publication year - 1995
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.1995.sp021033
Subject(s) - phenylephrine , isoprenaline , prazosin , medicine , endocrinology , forskolin , chemistry , alpha (finance) , antagonist , biology , stimulation , receptor , construct validity , nursing , blood pressure , patient satisfaction
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.