Crosstalk between presynaptic angiotensin receptors bradykinin receptors and α2-autoreceptors in sympathetic neurons: a study in α2-adrenoceptor-deficient mice

摘要

class="enumerated" style="list-style-type:decimal">In mouse atria, angiotensin II and bradykinin lose much or all of their noradrenaline release-enhancing effect when presynaptic α2-autoinhibition does not operate either because of stimulation with very brief pulse trains or because of treatment with α2 antagonists. We now studied this operational condition in α2-adrenoceptor-deficient mice. Release of ³H-noradrenaline was elicited by electrical stimulation.In tissues from wild-type (WT) mice, angiotensin II and bradykinin increased the overflow of tritium evoked by 120 pulses at 3 Hz. This enhancement did not occur or was much reduced when tissues were stimulated by 120 pulses at 3 Hz in the presence of rauwolscine and phentolamine, or when they were stimulated by 20 pulses at 50 Hz.In tissues from mice lacking the α2A-adrenoceptor (α2AKO) or the α2B-adrenoceptor (α2BKO), the concentration–response curves of angiotensin II and bradykinin (120 pulses at 3 Hz) were unchanged. In tissues from mice lacking the α2C-adrenoceptor (α2CKO) or both the α2A- and the α2C-adrenoceptor (α2ACKO), the concentration–response curves were shifted to the same extent downwards.As in WT tissues, angiotensin II and bradykinin lost most or all of their effect in α2AKO and α2ACKO tissues when rauwolscine and phentolamine were present or trains consisted of 20 pulses at 50 Hz.Rauwolscine and phentolamine increased tritium overflow evoked by 120 pulses at 3 Hz up to seven-fold in WT and α2BKO tissues, three-fold in α2AKO and α_2CKO tissues, and two-fold in α_2ACKO tissues.Results confirm that angiotensin II and bradykinin require ongoing α₂-autoinhibition for the full extent of their release-enhancing effect. Specifically, they require ongoing α_2C-autoinhibition. The peptide effects that remain in α_2C-autoreceptor-deficient mice seem to be because of α_2B-autoinhibition. The results hence also suggest that in addition to α_2A- and α_2C- mouse postganglionic sympathetic neurons possess α_2B-autoreceptors.