Developmental Changes in Agonist-Mediated Gastric Smooth Muscle Contraction in the Rabbit

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Abstract
We studied smooth muscle strips from rabbit proximal stomach to explore the age-related changes in agonist-mediated contraction. Strips from neonatal (1 d) and weanling (11 wk) rabbits were oriented to measure isometric tension in circular muscle. Bethanechol stimulated maximal tension in both age groups. Although the potencies for bethanechol were similar (ED50 ∼5 μM), the maximal response was nearly 4-fold greater in weanling (1140 ± 73 mN/cm2) versus neonate (305 ± 54 mN/cm2), p < 0.001. Maximum stress increased with age for bethanechol, high extracellular K+, and substance P, but not for serotonin, cholecystokinin octapeptide, neurotensin, or bombesin. Only bombesin stimulated larger contraction in neonates (152 ± 37 mN/cm2) versus weanlings (86 ± 20 mN/cm2), p < 0.05. Potencies did not change with age, except for substance P and serotonin. Substance P and serotonin induced early phasic and prolonged tonic contractions, which were unaffected by tetrodotoxin or atropine. ED50 for the phasic and tonic components of substance P-stimulated contraction in neonates were 1.8 and 7.7 nM. Substance P was 60-70 times more potent in neonates versus weanlings (p < 0.001). ED50 for serotoninstimulated contraction in neonates (33 and 22 nM, respectively) were 20-30 times more potent than in weanlings (p < 0.05). Motilin, morphine, epidermal growth factor, and gastrin did not stimulate contraction at either age. We conclude that age-dependent changes in agonist potency and efficacy may be one factor to explain in part the changes that occur in gastric motility during postnatal development.

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