Studies on Quinine and Quinidine V. Do They Have a Specific Action on Autonomic Nerve Ends?

Abstract

499foetal life. Sixteen, 17, and 18-day embryos were similarly injected. Gonads of both sexes were preserved for sectioning at various stages of both injected and non-injected animals. All material was fixed in Bouin's solution.Prenatal injection in no way hastened the differentiation in the gonad. It is thus evident that the gonad of the rat foetus is i n c a p able of response to the pituitary hormone. No evidence of sexual maturity was observed in either sex until the tenth day of postnatal life, when the effect was most pronounced in the male. This effect evinced itself in an apparent increase in tubule length as well as by a considerable thickening of the tubular wall. There is an undoubted increase in the size of the interstitial cells, and the tissue presents a dense and closely-packed appearance. We attribute this close-packed appearance to the increase in length and diameter of the tubules. No reconstructions have as yet been made to render this point a certainty.In the ovary the earliest advance in maturity of the injected animals over the controls appeared at approximately the fifteenth day. No corpora lutea were present but the follicles are larger in diameter and more nearly approaching maturity than in the normal animal if judged by the amount of follicular fluid present. At the twentieth day this precocious development is more marked. In no case were corpora lutea observed nor could eggs be discerned within the lumen of the sectioned tube.On the basis of the above results, the physiological effect of the pituitary hormone upon the gonad first shows itself in both. sexes between the tenth and fifteenth days of postnatal life.

Quinidine is a competitive antagonist at alpha 1- and alpha 2-adrenergic receptors.

“…Although it has been known for over 50 years that quinidine can block some adrenergic-mediated responses (Nelson, 1928), the mechanism has not been clearly defined. Our results demonstate that quinidine is a competitive antagonist of a^-and a.ireceptors in several tissues, with a dissociation constant (concentration required to bind half the receptors) of 1-3 fiM.…”

“…In addition to its wellknown direct effects on myocardial excitability, conduction velocity, and contractility, quinidine also has indirect effects on the cardiovascular system, including anticholinergic and antiadrenergic actions (c.f. Nelson, 1928;Hiatt, 1950;James andNadeau, 1967, Schmid et al, 1974;Mirro et al, 1980;Toda et al, 1981, Caldwell et al, 1983. The anticholinergic effects on the heart appear to result from blockade of muscarinic receptors (Mirro et al, 1980), but the mechanism by which quinidine exerts its antiadrenergic actions has not been clearly defined.…”