Effect of alpha2-adrenoceptor stimulation on isolated canine Purkinje fiber contraction.
We have recently identified the presence of postjunctional alpha2-adrenoceptors in canine Purkinje fibers. In this study, we examined the effects of alpha2-adrenoceptor stimulation on the contraction strength of isolated Purkinje fibers. Exposure to the alpha2-adrenoceptor specific agonist and antagonist, UK 14,304 (5-bromo-N-(4,5-dihydro-1H-imidazol-2-yl)-6-quinoxalinamine) and yohimbine (17-hydroxyyohimban-16-carboxylic acid methyl ester hydrochloride) alone at 0.1 microM respectively, did not produce any significant effect on Purkinje contraction strength. Purkinje contraction strength was augmented by isoproterenol (0.1 microM), forskolin (0.1 microM), or 8-bromo-adenosine cyclic 2',3'-monophosphate (8-bromo-cAMP, 10 microM). UK 14,304 significantly reversed the effects of isoproterenol and forskolin but not those of 8-bromo-cAMP on Purkinje contraction strength. After incubation with pertussis toxin, the positive inotropic effect of forskolin on Purkinje contraction strength remained intact, but the forskolin effect could no longer be reversed by UK 14,304. These results suggest that the postjunctional alpha2-adrenoceptors in canine Purkinje fibers are coupled to a pertussis toxin-sensitive G protein, probably Gi. Stimulation of the alpha2-adrenoceptor antagonizes the effect of beta-adrenoceptor stimulation on Purkinje contraction strength in an accentuated antagonism manner.
Stephenson
R S
RS
Department of Pediatrics, College of Medicine, the University of Iowa, Iowa City 52242, USA.
Cai
J J
JJ
Drews
T A
TA
Lee
H C
HC
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D058647:Adrenergic alpha-2 Receptor Agonists; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D005576:Colforsin / Q000494:pharmacology; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004558:Electric Stimulation; D005260:Female; D006321:Heart / Q000294:innervation; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009200:Myocardial Contraction / Q000502:physiology*; D037342:Pertussis Toxin; D011690:Purkinje Fibers / Q000187:drug effects*; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D058647:Adrenergic alpha-2 Receptor Agonists; D000316:Adrenergic alpha-Agonists; D000318:Adrenergic beta-Agonists; D010566:Virulence Factors, Bordetella; D005576:Colforsin; D015124:8-Bromo Cyclic Adenosine Monophosphate; D037342:Pertussis Toxin; D007545:Isoproterenol