Alterations in prejunctional adrenoceptor function in guinea pig and rat vas deferens after chronic ganglionic blockade.

The purpose of the present study was to test the hypothesis that alterations in nerve impulse traffic can influence the activity of substances which act prejunctionally to alter adrenergic neurotransmission. Measurements of the rapid phasic contraction of the isolated rat or guinea-pig vas deferens to short periods of electrical field stimulation were carried out in tissues obtained from saline- or chorisondamine-treated (8 mg/kg twice daily for 5 days) rats and guinea pigs. The alpha-2 selective agonist and antagonist, clonidine, and yohimbine, respectively, were utilized to assess prejunctional alpha-adrenergic function. It was observed that chronic treatment with chlorisondamine in doses that blocked ganglionic transmission produced a subsensitivity of the prejunctional alpha adrenoceptor system as evidenced by the fact that both the alpha-2 agonist, clonidine, and the alpha-2 antagonist, yohimbine, were less effective in decreasing or increasing nerve-stimulated induced contractions of the vas deferens, respectively. The present results are consistent with the idea that interruption of nerve impulse traffic results in a loss or decrease in the function or prejunctional inhibitory systems. Postjunctional supersensitivity of effector cells is an adaptive change in the direction of compensating for a decline in exposure to the neurotransmitter. The physiological success of the adaptation would be further enhanced by an increase in transmitter release consequent to subsensitivity of the presynaptic feedback inhibition.

Incorporation of 5-lododeoxyuridine into the DNA of mouse embryos: its relation to embryotoxicity.

Pregnant female ICR mice were administered, ip, either a trace (200 muCi/kg) or teratogenic (200 muCi + 300 mg/kg) dose of [6(-3)H] 5-iododeoxyuridine (IdU) on day 10 of gestation. Maternal liver, spleen, intestine, and kidneys, and placentas and embryos were removed at various time intervals after injection, weighed, and homogenized in cold 0.5 m perchloric acid. The half-lives of IdU-derived nucleotides in the acid-soluble fraction ranged from 31-46 min (trace) to 57-131 min (teratogenic) for the tissues analyzed. [3H]IdU was incorporated into the DNA of all mitotically active tissues after both dosages. The presence of the label in iodouracil was demonstrated by thin-layer chromatography of DNA bases extracted from maternal spleen and embryo. Growth of embryos following injection on day 10 resulted in decreased 3H-specific activity in the DNA fraction and concomitant retention of total activity. It is suggested that the previously demonstrated embryotoxicity of IdU is related to its retention at its presumed intracellular site of action.