METHOXAMINE AS A TOOL TO ASSESS THE IMPORTANCE OF INTRANEURONAL UPTAKE OF l-NOREPINEPHRINE IN THE CAT's NICTITATING MEMBRANE

TL;DR: The results support the view that, in the cat's nictitating membrane, intraneuronal uptake has a decisive influence on the concentration of norepinephrine at the receptors.

Abstract: Isolated rabbit aortic strips were exposed to methoxamine-H3. Its retention was negligible under conditions which led to considerable retention of norepinephrine-H3. Since intraneuronal uptake of methoxamine seems to be very small, the amine was used to test various postulates arising out of the concept that, in the nictitating membrane of the cat, intraneuronal uptake is the most important factor influencing the concentration of l -norepinephrine at the receptors. On the nictitating membrane, methoxamine has a direct effect. In agreement with postulates, cocaine or denervation failed to cause supersensitivity to methoxamine under experimental conditions which are known to produce pronounced supersensitivity to l -norepinephrine. Decentralization supersensitivity, on the other hand, was equally pronounced for both amines; this observation supports the view that decentralization supersensitivity is due to a postsynaptic event. On the normal and on the denervated isolated nictitating membrane the antagonism of phentolamine to methoxamine was of the competitive type. Earlier observations, on the other hand, had shown that the antagonism of phentolamine to l -norepinephrine appeared not to be competitive when the intraneuronal uptake mechanism was intact. The results support the view that, in the cat's nictitating membrane, intraneuronal uptake has a decisive influence on the concentration of norepinephrine at the receptors. Chronic decentralization or chronic denervation caused a decrease in the slopes of dose-response curves for methoxamine; apparently, saturation of uptake is not the only determinant of slopes of dose response curves for sympathomimetic amines.