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Antagonism between (–)‐N 6 ‐phenylisopropyl‐adenosine and the calcium channel facilitator Bay K 8644, on guinea‐pig isolated atria
Author(s) -
Caparrotta L.,
Fassina G.,
Froldi G.,
Poja R.
Publication year - 1987
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1987.tb16821.x
Subject(s) - chronotropic , medicine , chemistry , endocrinology , guinea pig , carbachol , calcium , reserpine , methoxamine , nitrendipine , adenosine , biology , agonist , stimulation , receptor , heart rate , blood pressure
1 Antagonism between (–)‐N 6 ‐phenylisopropyladenosine (PIA) and the dihydropyridine calcium channel facilitator Bay K 8644 was investigated in guinea‐pig spontaneously beating or electrically driven isolated atria, taken from normal and from reserpine‐treated animals. 2 PIA (3–100 n m ) produced a dose‐dependent decrease in contractile tension and frequency in spontaneously beating atria being more effective in reserpinized preparations. 3 Bay K 8644 (5–200 n m ) produced an increase in contractile tension in both normal and reserpinized atria. In electrically driven left atria the positive inotropic effect of Bay K 8644 was similar to that in spontaneously beating preparations. The positive chronotropic effect of Bay K 8644 was slight and variable. 4 PIA produced a rightward parallel shift of the concentration‐response curves for the positive inotropic effects of Bay K 8644 in all experimental conditions. In spontaneously beating atria from normal guinea‐pigs, the Schild regression plot was linear and its slope near to unity; pA 2 of PIA 8.63 ± 0.05 (IC 50 2.35 ± 0.25 n m ). In electrically driven atria the antagonism by PIA of the effects of Bay K 8644 was apparently competitive, and the IC 50 of PIA was 18.6 ± 0.4 n M . PIA antagonized the positive chronotropic effect of Bay K 8644 in spontaneously beating preparations, both from normal and from reserpine‐treated animals. 5 Carbachol did not modify the positive inotropic effects of Bay K 8644. 6 These data indicate that PIA may interact with Bay K 8644 at the level of the slow calcium channels, and may decrease the transmembrane calcium flux into the cell.