13 367

Cited 0 times in

Cocaine과 norepinephrine과의 相協作用에 關한 硏究

Other Titles
 Studies on the mechanism of norepinephrine supersensitivity by cocaine 
Authors
 김두현 
Issue Date
1966
Description
의학과/박사
Abstract
[한글]

[영문]

Since Frohlich and Loewi (1910) first described sensitization by cocaine of various organs to epinephrine, different explanations for the potentiating effect of cocaine on responses to epinephrine or norepinephrine have been offered. The early suggestion of Torda(1943) concerning cocaine potentiation was that cocaine delays the inactivation of epinephrine and norepinephrine so that following the injection of a given dose the concentration at the receptors would be higher.

Later, Burn(1952b) postulated that this action of cocaine had been thought to be responsible for the supersensitivity to norepinephrine, since cocaine was found to inhibit amine oxidase(philpot, 1940). On the other hand, Fleckenstein and

Bass(1953) pointed out that cocaine caused "pharmacological denervation" by inhibiting the release of norepinephrine from postganglionic nerve endings and thus increased the sensitivity of the nictitating membrane. Furthermore, Trendelenburg(1959) suggested that cocaine increased the sensitivity by delaying

the inactivation of norepinephrine and thin inactivation was possibly due to the tissue binding of norepinephrine.

Since the recent investigations have demonstrated a rapid uptake of injected norepinephrine by various tissues(Muscholl, 1961; Kopin et al., 1962), and this uptake was been thought to be the most important mechanism of rapid inactivation, the potentiating action of cocaine has been explained on the basis of its ability to block norepinephrine uptake in tissue(MacMillan, 1959).

Nevertheless of these numerous investigations, the precise mechanism whereby cocaine sensitizes the cardiac muscle to norepinephrine is poorly understood. The present experiment was therefore performed further to elucidate the nature of norepinephrine supersensitivity by cocaine in cardiac tissue, with special reference to myocardial catecholamines.

Methods

Atria isolated from rabbits treated with various drugs were employed in this experiment. The heart was rapidly removed from rabbits under ether anesthesia. The atria isolated from ventricles, were suspended in a constant temperature(38℃) bath

containing 100 ml Tyrode solution aerated with 95% oxygen and 5% carbon dioxide.

The spontaneous contractile amplitude was recorded with a isotonic lever. Drugs were added to the bath and the changes of contractile amplitude and rate of spontaneous beat were expressed as per cent changes relative to those prior to the addition of the drugs. The catecholamine content of cardiac muscle was determined by the spectrophotofluorometric procedure described by Shore and Olin(1958). MAO activity was determined colorimedtrically according to the procedure of Green and

Haughton(1961).

Results

1. Normal: Cocaine exerted little or no effects on the isolates atria from normal rabbits at concentrations below 3×10**-5 M. However, following the administration of cocaine(10**-5 M), the cardiostimulant response of the atria to norepinephrine was markedly augmented. Similar augmentation of the cardiostimulant activity of norepinephrine was observed in the atria pretreated with cocaine and SKF-385(10**-5 M) which has completely inhibited the monoamine oxidase activity in the cardiac tissues. After pretreatment of pyrogallol(10**-5 M) and cocaine, the augmentation of activity of norepinephrine was also similar to that seen in the atria of rabbits treated with cocaine alone. Consequently, the administration of both SKF-385 and pyrogallol did not significantly mortify the cardiostimulant response of the atria to norepinephrine in the presence of cocaine. This result suggests that augmentation of the activity of norepinephrine is due to neither the suppression of MAO-activity nor the inhibition of COMT in these atria.

2. Reserpine treated: Reserpine(3.Omg/kg) was injected intraperitoneally into rabbits and the animals were killed 24 hours after the injection. The myocardial catecholamine content of these animals was markedly depleted. In the presence of cocaine, the cardiostimulant response of the atria to norepinephrine was not significantly different from those observed in normal atria. Examination of catecholamine content of atria after exposure of norepinephrine (3×10**-7 ) revealed an average 0.25 μg/g. This value is significantly higher than the mean value of unexposed atria, 0.08μg/g. Whereas, in the presence of cocaine catecholamine content of these atria was significantly decreased to 0.15 μg/g. After inhibition of monoamine oxidase activity by the administration of SKF-385,

augmentation of activity of norepinephrine was similar to that seen in those atria treated with cocaine alone. However, following the administration of cocaine the cardiostimulant response of those atria to norepinephrine was most markedly

pronounced.

3. Norepinephrine treated: The injection of norepinephrine(2.Omg/kg) markedly elevated the concentration of myocardial catecholamines in rabbits. The cardiostimulant response of the atria to norepinephrine was greatly reduced as compared with those of normal and reserpine treated atria. Following the administration of cocaine, the augmentation of activity of norepinephrine was observed in these atria. However this augmentation was far below level than those seen in normal and reserpine treated atria.

From the above results, it may be concluded that the ability of cocaine to potentiate the activity of norepinephrine in a cardiac tissue depends on the extent to which the amine is inactivated in that tissue by an uptake mechanism which is sensitive to inhibit by cocaine. Furthermore this result also suggested that the augmentation of activity of norepinephrine by cocaine is closely related to the quantitative changes of the endogenous myocardial catecholamine content.
Full Text
https://ymlib.yonsei.ac.kr/catalog/search/book-detail/?cid=CAT000000044481
Files in This Item:
제한공개 원문입니다.
Appears in Collections:
1. College of Medicine (의과대학) > Others (기타) > 3. Dissertation
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/126597
사서에게 알리기
  feedback

qrcode

Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.

Browse

Links