Sensitivity of the isolated vas deferens of the guinea-pig to norepinephrine and acetylcholine after denervation, decentralization and treatments by various agents

Abstract

The sensitivity of the isolated vas deferens of the guinea-pig to norepinephrine (NE) and acetylcholine (ACh) after various treatments was examined and the following results were obtained. The sensitivity of the isolated vas deferens to NE was markedly increased at 2, 7 and 28 days after denervation and by cocaine 10 −6M or hexylguanidine 10 −4M. It was moderately increased by long-term treatment with reserpine (0.1 mg/kg/day for 7–14 days) or guanethidine (10 mg/kg/day for 7 days). Supersensitivity after denervation appeared after 2 days and reached a maximum about 7 days after operation. The onset of supersensitivity after denervation was more rapid than after cocaine or hexylguanidine. The sensitivity to NE was decreased by treatment with tetrodotoxin (0.5–2 μg/kg/day for 14–28 days) or by cold storage (6–8°C, for 7 days). Sensitivity to NE was not affected 7 and 28 days after decentralization or by short-term treatment with reserpine (3 mg/kg, 24 hr prior to experiment, 1 mg/kg/day for 2 days), hexamethonium (2–5 mg/kg/day, twice daily) or tetrodotoxin (0.1–2 gmg/kg/day for 7 days). Cocaine increased supersensitivity after denervation and after cold storage. The sensitivity of the isolated vas deferens to ACh was not changed by any of the afore mentioned treatments and procedures except for cold storage. It is concluded that the supersensitivity of the guinea-pig isolated vas deferens after various treatments is specific for NE, and that the supersensitivity is mainly due to the impairment of NE uptake into the adrenergic nerve endings, but a postsynaptic mechanism cannot be excluded.