摘要:

SUMMARY1 KCl produced a biphasic contraction in the intact rat vas deferens. Both components were larger and the initial rapid phasic component was faster in the prostatic portion than the epididymal portion. In some experiments the epididymal phasic response was a single slow contraction, while in others it had a mixture of fast and slow responses.2 Phentolamine reduced the phasic response but not the tonic response of the intact vas deferens. This effect was not observed after denervation produced by chronic guanethidine treatment.3 Both phases of the response to KC1 160 mmol/1 were substantially reduced by phentolamine in the epididymal portion. In the prostatic portion phentolamine produced only slight inhibition of the phasic component and had no effect on the tonic component.4 Isoprenaline had no effect on the response to KC1160 mmol/1 but reduced both phases of the response to KC150 mmol/1. This effect was antagonized by propranolol.5 It is concluded that part of the phasic component of the response to KC1 in the rat vas deferens is due to the release of noradrenaline from intramural nerves.

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1983.tb00174.x

出版商:Blackwell Publishing Ltd    

年代:1983

数据来源: WILEY

摘要:

ABSTRACTHistorically, the concept of metabolic activation was first forwarded to explain thein vivoactivity of certain carcinogenic chemicals that without prior metabolism were chemically inert and biologically inactive. Subsequently, the concept has been extended to explain the effects of many different classes of chemicals causing diverse toxicities. Because of its major role in drug metabolism, the liver is a prominent site for toxic injury by agents requiring metabolic activation. The liver can also be the source of reactive metabolites that damage extrahepatic organs. But, organ selective toxicity can also result from thein situmetabolic activation of foreign chemicals in extrahepatic target tissues such as the lungs and the kidneys. Moreover, extrahepatic tissues generally are much more heterogeneous in cellular composition compared to the liver, and the localization of drug metabolizing enzymes in certain cell populations may result in highly cell selective toxic injury. The significance of metabolic activation and toxicity–and the importance of the particular chemical structure of individual compounds, as well as host factors such as species, age, sex, and pretreatment effects –on target‐organ‐selective toxicity by reactive metabolites are illustrated by studies with various furan derivatives, an important class of environmental chemicals.SUMMARYTo conclude this paper, we should simply like to restate the major points we have attempted to illustrate herein: (a) some general concepts concerning the relationships between metabolic activation, reactive intermediates, and toxicity; (b) the potential involvement of metabolic activation both in hepatic and in extrahepatic toxicities; (c) a consideration of chemical/structural factors and host factors (e.g. species, strain, sex, age, pretreatments) affecting target organ selectivity, exemplified by furan compounds; and (d) the importance of cellular specificity for metabolism and toxicity in extrahepatic tissues, as exemplified for pulmonary Clara cells with the pulmonary toxin 4‐

ISSN:0305-1870    

DOI:10.1111/j.1440-1681.1983.tb00175.x

出版商:Blackwell Publishing Ltd    

年代:1983

数据来源: WILEY