Presynaptic modulation of release of noradrenaline from the sympathetic nerve terminals in the rat spleen.

Strips of rat spleen, loaded with [3H]NA, were superfused with Krebs' stimulated electrically at different frequencies (2, 8 and 32 Hz) with the same number of pulses and the effect of different receptor agonists and antagonists was studied on the S2/S1 ratio. Evidence has been obtained that the sympathetic nerve terminals in the spleen of the rat are equipped with presynaptic alpha 2B-adrenoreceptors, M-muscarinic, N-nicotinic and P1-purinoreceptors. Clonidine, an alpha 2-adrenoreceptor agonist, did not change the release of NA at low frequency but increased it at a high frequency of stimulation. It is suggested that clonidine is a partial agonist and reveals its antagonistic property when the biophase concentration of the full agonist, NA, released endogenously large. A novel, potent and highly selective competitive antagonist of the alpha 2-adrenoreceptor, CH-38083, enhanced significantly the release of NA, removing presynaptic negative feedback control of NA. It is suggested that the release of NA is subject to presynaptic modulation, through different presynaptic receptors and that it is involved in the communication between the central nervous system and a secondary lymphoid organ, the spleen.