RT Journal Article
SR Electronic
T1 MECHANISMS OF SYMPATHOMIMETIC EFFECTS OF DICHLOROISOPROTERENOL: COMPARISON WITH TYRAMINE, NICOTINE AND NOREPINEPHRINE
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 135
OP 142
VO 157
IS 1
A1 Naranjan S. Dhalla
YR 1967
UL http://jpet.aspetjournals.org/content/157/1/135.abstract
AB Pretreatment of rats with reserpine abolished the phosphorylase activation by dichloroisoproterenol (DCI) in the atria but not in the diaphragm. These results support our earlier view that the sympathomimetic actions of DCI in vivo are due to both direct and indirect adrenergic mechanisms. On electrically driven rat atria, the positive inotropic effect of DCI and nicotine, but not of tyramine or norepinephrine (NE), was inhibited by morphine, imipramine, iproniazid, tranylcypromine and hexamethonium. The effects of DCI, tyramine and nicotine were blocked by both propranolol and cocaine, whereas the action of NE was potentiated by cocaine and antagonized by propranolol. On spontaneously beating rat atria, pentolinium, hemicholinium, phenoxybenzamine, methyl derivative of xylylcholine ether (βTM 10) and chlorobenzyl dimethylguanidine (BW392C60) inhibited the positive inotropic and chronotropic actions of DCI and nicotine but did not alter the effects of tyramine or NE. Isopropylamino-hydroxyethyl methanesulfonanalide (MJ 1999) antagonized the cardiostimulant effects of DCI, tyramine, nicotine and NE whereas atropine and piperoxan were ineffective. When the atria were made tachyphylactic to tyramine, DCI and nicotine, unlike NE, failed to produce sympathomimetic actions. These results indicate that the mode of action of DCI is similar to that of nicotine rather than tyramine. It is suggested that drug-induced release of NE may be produced either by replacement mechanism represented by tyramine or by depolarization of the sympathetic nerve terminal as in the case of nicotine or DCI. © 1967 by The Williams & Wilkins Company