Journal of Applied Physiology, Vol 64, Issue 6 2501-2507, Copyright © 1988 by American Physiological Society
Antagonism of relaxation to isoproterenol caused by agonist interactions
S. R. White, K. J. Popovich, R. W. Mitchell, S. M. Koenig, M. M. Mack, N. M. Munoz and A. R. Leff
Department of Medicine, University of Chicago, Illinois 60637.
The interaction of contractile agonists on the relaxation elicited with
isoproterenol (ISO) was studied in 112 tracheal smooth muscle (TSM) strips
from 20 dogs in vitro. Strips were contracted to the same active target
tension (TT) with acetylcholine (ACh), histamine (HIS), serotonin
(5-hydroxytryptamine, 5-HT), potassium chloride (KCl), or the combinations
of ACh + HIS, ACh + 5-HT, HIS + KCl, HIS + 5-HT (50% TT from each agonist).
Although a less potent agonist, adding HIS to cause 50% of the TT reduced
the concentration of ACh to elicit the remaining 50% TT and substantially
altered relaxation by ISO compared with HIS alone [concentration required
to achieve 50% relaxation (RC50) = 9.2 +/- 2.4 X 10(-8) vs. 9.0 +/- 4.4 X
10(-9) M to HIS alone; P less than 0.003]. Relaxation for TSM strips
contracted with ACh + HIS was comparable to that elicited from the same TT
with ACh alone, although concentrations required in combination were lower
than for either agonist alone. Trachealis strips contracted equivalently
with KCl + HIS also had augmented contraction and attenuated relaxation
(RC50 = 3.7 +/- 0.8 X 10(-8) M; P less than 0.015 vs. HIS alone). However,
combinations of 5-HT + ACh and 5-HT + HIS did not alter relaxation to ISO
from that elicited by the weaker agonist alone. We demonstrate that TSM
relaxation depends on the combination of agonists eliciting contraction and
may be inhibited substantially by interactions among contractile agonists.
