AJP - Gastrointestinal and Liver Physiology, Vol 262, Issue 2 291-G297, Copyright © 1992 by American Physiological Society
Postnatal changes in the substance P receptor on rabbit gastric smooth muscle
P. E. Hyman, S. Kimura, T. Tomomasa, Q. X. Yuan, W. J. Snape Jr and J. A. McRoberts
Department of Pediatrics, Harbor-UCLA Medical Center, Torrance 90502.
We used radioligand binding to tissue homogenates and isometric contraction
of muscle strips to characterize the substance P (SP) receptor on gastric
smooth muscle from 1- (newborn) and 7-day-old and 4- and 11-wk-old
(weanling) rabbits. Scatchard analysis for newborns was curvilinear,
suggesting the presence of multiple binding sites. In newborns the
dissociation constant (Kd) of high-affinity binding site was 2.2 +/- 0.3
nM, and the maximum binding (Bmax) was 0.57 +/- 0.06 pmol/mg DNA. The
number of high-affinity binding sites decreased with age, disappearing by
11 wk. The Kd for the low-affinity site was more than two orders of
magnitude greater than that of the high-affinity site. In competitive
binding studies with [3H]SP, the order of potency for the neurokinins was
SP much greater than neurokinin A (NKA) greater than neurokinin B (NKB),
suggesting that the high-affinity binding sites were NK-1 receptors.
[125I]NKA is also bound to newborn tissue homogenate with high affinity.
With [125I]NKA the order was NKA greater than SP greater than NKB,
suggesting that NK-2 receptors were also present. In contraction studies,
atropine and tetrodotoxin had no effect on tachykinin-stimulated
contraction, suggesting solely myogenic tachykinin effects on this tissue.
In newborn rabbits, the potency and efficacy of SP and NKA were similar.
The half-maximal effective dose (ED50) of SP was nearly two orders of
magnitude less in newborn rabbits than in weanlings; the potency of NKA did
not change.(ABSTRACT TRUNCATED AT 250 WORDS)
