Prostaglandin-mediated inhibition of noradrenaline release: II. Dual mechanism behind its frequency-dependence

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Abstract
Sympathetically innervated, isolated rabbit hearts were perfused according to Langendorff and the nerves were stimulated at 2, 5 or 10 Hz by equally long trains of pulses. The outflows of prostaglandin-like substances (PLS) and of noradrenaline (NA), induced by the nerve stimulations, were followed. The sensitivity of the process of NA release to exogenous PG[prostaglandin]-E1 (2-6 .times. 10-8 M) at 2, 5 and 10 Hz was assayed. The outflow of PLS was frequency-dependent, being greater at 2 Hz than at higher discharge rates, while the outflow of NA was similar at the different frequencies. The inhibitory action of PGE1 on the NA release process was more pronounced at 2 than at 10 Hz. The frequency-dependence of the endogenous PGE-mediated inhibition of the release of NA from discharging sympathetic nerves is based on 2 independent, frequency-related mechanisms: a higher synthesis rate of PLS/impulse, and a more pronounced sensitivity of the process of NA release, at low compared to higher inpulse frequencies.

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