Species differences in the negative inotropic effect of acetylcholine and soman in rat, guinea pig, and rabbit hearts.
1. Acetylcholine reduced atrial contractions by 82.5% in guinea pig, 50.8% in rat, and 41.5% in rabbit. 2. The EC50 values for the negative inotropic effect of acetylcholine were 3.3 x 10(-7) M in rat and guinea pig atria and 4.1 x 10(-6) M in rabbit atria. 3. There was no correlation between the species differences in the negative inotropic effect of acetylcholine in atria and the density or affinity of acetylcholinesterase or muscarinic receptors. 4. Inhibition of atrial acetylcholinesterase with soman reduced the EC50 of acetylcholine three-fold in all species, but did not change the maximal inotropic effect of acetylcholine. 5. Species differences in the negative inotropic effect of acetylcholine may be caused by differences in the coupling between myocardial muscarinic receptors and the ion channels that mediate negative inotropy.
U.S. Army Medical Research Institute of Chemical Defense, Aberdeen Proving Ground, Maryland.
D M
DM
Maxwell
R H
RH
Thomsen
S I
SI
Baskin
D000109:Acetylcholine / Q000494:pharmacology*; D000110:Acetylcholinesterase / Q000378:metabolism*; D000818:Animals; D002802:Cholinesterases / Q000378:metabolism*; D003864:Depression, Chemical; D006168:Guinea Pigs; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains; D011976:Receptors, Muscarinic / Q000187:drug effects*; D012999:Soman / Q000494:pharmacology*; D013045:Species Specificity
D011976:Receptors, Muscarinic; D012999:Soman; D000110:Acetylcholinesterase; D002802:Cholinesterases; D000109:Acetylcholine