Journal of Applied Physiology, Vol 63, Issue 4 1396-1400, Copyright © 1987 by American Physiological Society
Cholinergic neuromodulation by prostaglandin D2 in canine airway smooth muscle
J. Tamaoki, K. Sekizawa, P. D. Graf and J. A. Nadel
Cardiovascular Research Institute, University of California, San Francisco 94143.
To determine whether prostaglandin D2 (PGD2) modulates cholinergic
neurotransmission in airway smooth muscle and, if so, what the mechanism of
action is, we studied bronchial segments from dogs under isometric
conditions in vitro. PGD2 (10(-8)-10(-5) M) elicited dose-dependent muscle
contraction, which was reduced after blockade of muscarinic receptors, so
that 50% effective dose (ED50) increased from 1.3 +/- 0.3 X 10(-6) to 3.9
+/- 1.0 X 10(-6) M by atropine (10(-6) M) (mean +/- SE, P less than 0.05).
Physostigmine, at a concentration insufficient to alter base-line tension
(10(-8) M), enhanced the PGD2-induced contraction and decreased ED50 to 6.4
+/- 0.5 X 10(-7) M (P less than 0.05). When added at the highest doses that
did not cause spontaneous contraction (1.9 +/- 0.5 X 10(-7) M), PGD2
increased the contractile response to electrical field stimulation (1-50
Hz) by 21.9 +/- 6.6% (P less than 0.001). In contrast to this effect, the
response to administered acetylcholine was not affected by PGD2. On the
other hand, PGD2-induced augmentation of the response to electrical field
stimulation (5 Hz) was further increased from 23.6 +/- 3.0 to 70.4 +/- 8.8%
in the presence of physostigmine (10(-8) M) and was abolished by atropine
but not affected by the alpha-adrenergic antagonist phentolamine or the
histamine H1-blocker pyrilamine. These results suggest that the contraction
of airway smooth muscle induced by PGD2 is in in part mediated by a
cholinergic action and that PGD2 prejunctionally augments the
parasympathetic contractile response, likely involving the accelerated
release of acetylcholine at the neuromuscular junction.
