The effect of phospholipase C on the responsiveness of cardiac receptors. I. Inhibition of the adrenergic inotropic response

Jean F Regal, F. E. Shideman

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Abstract

To determine if phospholipids play a role in the response of the heart to catecholamines, a crude preparation of phospholipase C (PLC) from Clostridium perfringens was used to perturb membrane lipids in the isolated spontaneously beating 5-day-old embryonic chick heart (ECH). PLC inhibited inotropic but not chronotropic responses to l-isoproterenol and l-norepinephrine. The inhibition was noncompetitive, was dependent on PLC concentration and was spontaneously reversible. The effect of the enzyme on the positive inotropic response to l-isoproterenol was prevented by prior dilution and aeration in Tyrode's solution for 5 min or boiling for 30 min. The inhibition required calcium and was prevented by phosphatidylcholine, indicating that it is due to the calcium-dependent enzyme PLC and not some other constituent of the enzyme preparation. Partial purification of the PLC preparation by gel filtration yielded fractions which both maximally inhibited the adrenergic inotropic response and contained most of the PLC activity. The inhibition was not due to θ-toxin, a membrane-active contaminant of the PLC preparation. No binding of fluorescently labeled PLC to the 5-day-old ECH was detected by fluorescence microscopy. Propranolol selectively prevented the effect of PLC on the adrenergic inotropic response. These findings indicate that a catalytically active PLC from C. perfringens, an enzyme known to be able to cleave phospholipids in intact membranes, inhibits the adrenergic inotropic response of the ECH without affecting the chronotropic response and without extensively binding to the 5-day-old ECH.

Original languageEnglish (US)
Pages (from-to)282-290
Number of pages9
JournalJournal of Pharmacology and Experimental Therapeutics
Volume214
Issue number2
StatePublished - Jan 1 1980

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