Rajani A P, Gulati O D
Department of Pharmacology, Medical College, Baroda, India.
Arch Int Pharmacodyn Ther. 1988 Mar-Apr;292:86-100.
In rat isolated anococcygeus muscle, dopamine (2.6 x 10(-11) M to 8.3 x 10(-10) M) produced a concentration-dependent inhibitory effect on field stimulated contractions. The effect of dopamine was blocked by pimozide (2.2 x 10(-8) M) but not by yohimbine (2.6 x 10(-10) M) or propranolol (1.0 x 10(-7) M), suggesting a specific prejunctional inhibitory effect. Higher concentrations of dopamine (1.4 x 10(-7) M to 1.4 x 10(-4) M) elicited concentration-dependent contractions which were blocked competitively with higher concentrations of pimozide (2.2 x 10(-7) M to 1.4 x 10(-4) M) and 2.2 x 10(-6) M), suggesting a postjunctional activity. ACh in very low concentrations (2.8 x 10(-11) M to 4.4 x 10(-10) M) blocked the field stimulated contractions. Atropine (2.6 x 10(-9) M) per se augmented them and also antagonized the inhibitory effects of ACh, suggesting a prejunctional activity of ACh. Higher concentrations of ACh (5.5 x 10(-7) M to 7.0 x 10(-5) M) produced contractions which were not altered by atropine in a concentration (2.6 x 10(-9) M) which antagonized the prejunctional activity of ACh. Histamine, in a wide range (3.1 x 10(-12) M to 2.6 x 10(-8) M), did not modify field stimulated contractions. Very low concentrations of 5-HT (1.2 x 10(-11) M to 3.8 x 10(-10) M) had an inhibitory effect on field stimulated contractions. Methysergide (2.8 x 10(-9) M) enhanced the responses to electrical stimulation and antagonized the 5-HT-induced inhibitory effect. Still higher concentrations of 5-HT (1.9 x 10(-6) M to 1.0 x 10(-3) M) produced concentration-dependent contractions. Methysergide (8.5 x 10(-7) M) failed to antagonize, whereas phentolamine (1.0 x 10(-6) M) antagonized 5-HT competitively. Dopamine (8.3 x 10(-10) M), ACh (4.4 x 10(-10) M) or 5-HT (3.9 x 10(-10) M), in concentrations which produced a maximal prejunctional inhibitory effect, did not alter the EC50 value of NA, ruling out a post-junctional effect. Moreover, the concentration ratios of these agents for EC50 pre to EC50 post were less than 1, suggesting their preferential prejunctional site of action. It is concluded that multiple prejunctional site of action. It is concluded that multiple prejunctional receptor activities for DA, ACh (muscarinic) and 5-HT, which modify the release of neurotransmitter, may be operative in this preparation.
在大鼠离体肛门尾骨肌中，多巴胺（2.6×10⁻¹¹ M至8.3×10⁻¹⁰ M）对场刺激收缩产生浓度依赖性抑制作用。多巴胺的作用被匹莫齐特（2.2×10⁻⁸ M）阻断，但未被育亨宾（2.6×10⁻¹⁰ M）或普萘洛尔（1.0×10⁻⁷ M）阻断，提示存在特异性的接头前抑制作用。较高浓度的多巴胺（1.4×10⁻⁷ M至1.4×10⁻⁴ M）引起浓度依赖性收缩，该收缩被较高浓度的匹莫齐特（2.2×10⁻⁷ M至1.4×10⁻⁴ M）和2.2×10⁻⁶ M竞争性阻断，提示存在接头后活性。极低浓度的乙酰胆碱（2.8×10⁻¹¹ M至4.4×10⁻¹⁰ M）阻断场刺激收缩。阿托品（2.6×10⁻⁹ M）本身增强收缩，且拮抗乙酰胆碱的抑制作用，提示乙酰胆碱存在接头前活性。较高浓度的乙酰胆碱（5.5×10⁻⁷ M至7.0×10⁻⁵ M）产生的收缩不受阿托品（2.6×10⁻⁹ M，该浓度可拮抗乙酰胆碱的接头前活性）影响。组胺在较宽范围（3.1×10⁻¹² M至2.6×10⁻⁸ M）内不改变场刺激收缩。极低浓度的5-羟色胺（1.2×10⁻¹¹ M至3.8×10⁻¹⁰ M）对场刺激收缩有抑制作用。美西麦角（2.8×10⁻⁹ M）增强对电刺激的反应，并拮抗5-羟色胺诱导的抑制作用。更高浓度的5-羟色胺（1.9×10⁻⁶ M至1.0×10⁻³ M）产生浓度依赖性收缩。美西麦角（8.5×10⁻⁷ M）未能拮抗，而酚妥拉明（1.0×10⁻⁶ M）竞争性拮抗5-羟色胺。产生最大接头前抑制作用浓度的多巴胺（8.3×10⁻¹⁰ M）、乙酰胆碱（4.4×10⁻¹⁰ M）或5-羟色胺（3.9×10⁻¹⁰ M）不改变去甲肾上腺素的半数有效浓度（EC50）值，排除接头后效应。此外，这些药物的接头前EC50与接头后EC50的浓度比小于1，提示它们优先作用于接头前部位。结论是存在多个接头前作用部位。结论是多巴胺、乙酰胆碱（毒蕈碱型）和5-羟色胺存在多个接头前受体活性，它们可调节神经递质释放，在该制剂中可能起作用。
