AJP - Gastrointestinal and Liver Physiology, Vol 254, Issue 5 680-G686, Copyright © 1988 by American Physiological Society
Development of the muscarinic receptor in rabbit gastric smooth muscle
T. Tomomasa, P. E. Hyman, C. T. Hsu, J. Jing and W. J. Snape Jr
Department of Pediatrics, Harbor-UCLA Medical Center, Torrance 90509.
We used binding of [N-methyl-3H]scopolamine ( [3H]-NMS) to tissue
homogenates and isometric contraction of muscle strips to characterize
perinatal changes in the muscarinic receptor on rabbit gastric smooth
muscle. In homogenates from fetal (28 days of gestation), 1-, 3-, and
7-day, 4- and 11-wk-old rabbits, specific binding was saturable and
temperature dependent, achieved equilibrium by 10 min at 30 degrees C, and
was linearly related to tissue concentration. Specific binding was 80 +/-
2% of total binding at 0.2 nM [3H]NMS. The number of binding sites was
120,000 receptors/cell, maximal during the first week of life compared with
the fetus or older animals. Affinity of [3H]NMS was highest in the first
week of life (Kd = 345 +/- 24 pM, 1 day old). Age did not affect Hill
coefficients or Ki values; secoverine and
4-diphenylacetoxy-N-methylpiperidine methiodide were 50-fold more potent
than pirenzepine. In muscle strips, bethanechol stimulated dose-dependent
atropine-inhibitable isometric contraction. The doses required for
half-maximal contraction were similar in both age groups (5-6 microM), but
maximal contraction was fivefold greater in weanlings compared with
neonates. Increasing extracellular potassium concentration resulted in
similar differences, suggesting that the differences were not receptor
related. These results suggest that well-differentiated M2-muscarinic
receptors are functional on rabbit gastric smooth muscle during the
perinatal period.
