| Abstrakt: |
The release by electrical field stimulation of H-noradrenaline from the adrenergic nerve endings in the rabbit aorta was studied in a special double-chambered organ bath. Independently of the frequency (1-10 Hz) and the number of pulses used (300-3,000 pulses), only 10-20% of the stimulation-evoked overflow of tritium (total evoked overflow) left the aortic wall via the intimal surface (intimal evoked overflow). The corresponding percentage value for the basal efflux was twice that for the evoked overflow, thus indicating that part of the radioactivity in the basal efflux originated from an extraneuronal compartment. The radioactivity in the total evoked overflow (in response to stimulation at 10 Hz) originated from at least two compartments (compartment I and II) with half times for efflux of about 2 and 6 min, respectively. In the intimal evoked overflow, compartment II (but not compartment I) was involved. When uptake was inhibited, 70% of the radioactivity in the intimal evoked overflow (stimulation at 1 Hz) consisted of metabolites, while unchanged amine prevailed by far in the total and adventitial evoked overflow, respectively. Additional inhibition of uptake thus had a striking effect only on the composition of the radioactivity in the intimal evoked overflow. The intimal surface was exposed to unlabelled noradrenaline in order to inhibit the evolked overflow of tritium (stimulation at 1 Hz; uptake inhibited). When uptake was inhibited additionally, the dose-response curve for the inhibitory effect of noradrenaline was shifted to the left by a factor of 4. Such a shift of the dose-response curve was not seen for noradrenaline applied to the adventitial surface. Furthermore, the IC for noradrenaline was 30 times higher when the intimal than when the adventitial surface was exposed to the amine (both uptake mechanisms inhibited). This difference is explained by the slow diffusion of noradrenaline through intima and media. It is concluded that intima and media (but not adventitia) represent important extraneuronal sites of loss, but also a diffusion barrier for noradrenaline. The structural properties of the aorta thus favour the access and exit of noradrenaline to and from the adrenergic nerve endings via the adventitia. Therefore, special experimental conditions are indicated to evaluate the role of uptake for the inactivation of that noradrenaline which has diffused into intima and media on its way to or from the adrenergic nerve endings. [ABSTRACT FROM AUTHOR] |
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