Tomomasa T, Yagi H, Kimura S, Snape W J, Hyman P E
Department of Pediatrics and Medicine, Harbor-UCLA Medical Center, Torrance 90509.
Pediatr Res. 1989 Nov;26(5):458-61. doi: 10.1203/00006450-198911000-00019.
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 approximately 5 microM), the maximal response was nearly 4-fold greater in weanling (1140 +/- 73 mN/cm2) versus neonate (305 +/- 54 mN/cm2), p less than 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 less than 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 less than 0.001). ED50 for serotonin-stimulated contraction in neonates (33 and 22 nM, respectively) were 20-30 times more potent than in weanlings (p less than 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.
我们研究了兔近端胃的平滑肌条，以探索激动剂介导的收缩中与年龄相关的变化。取新生（1日龄）和断奶（11周龄）兔的平滑肌条，使其取向以测量环形肌的等长张力。氨甲酰甲胆碱刺激了两个年龄组的最大张力。虽然氨甲酰甲胆碱的效价相似（半数有效量约为5微摩尔），但断奶兔（1140±73毫牛顿/平方厘米）的最大反应比新生兔（305±54毫牛顿/平方厘米）大近4倍，P＜0.001。氨甲酰甲胆碱、高细胞外钾离子和P物质的最大应力随年龄增加，但5-羟色胺、胆囊收缩素八肽、神经降压素或蛙皮素则不然。只有蛙皮素刺激新生兔（152±37毫牛顿/平方厘米）的收缩比断奶兔（86±20毫牛顿/平方厘米）更大，P＜0.05。除P物质和5-羟色胺外，效价不随年龄变化。P物质和5-羟色胺诱导早期相性收缩和持续性强直性收缩，不受河豚毒素或阿托品影响。新生兔中P物质刺激收缩的相性和强直性成分的半数有效量分别为1.8和7.7纳摩尔。P物质在新生兔中的效价比断奶兔高60-70倍（P＜0.001）。新生兔中5-羟色胺刺激收缩的半数有效量（分别为33和22纳摩尔）比断奶兔高20-30倍（P＜0.05）。胃动素、吗啡、表皮生长因子和胃泌素在两个年龄组均未刺激收缩。我们得出结论，激动剂效价和效力的年龄依赖性变化可能是部分解释出生后发育过程中胃动力变化的一个因素。
