Facilitatory effect of adrenocorticotropic hormone and related peptides on ca2+-dependent noradrenaline release from sympathetic nerves

Strips of rabbit pulmonary artery and aorta were incubated with [ ³H]noradrenaline and subsequently superfused. Tritium overflow from strips superfused with physiological salt solution was stimulated either electrically (usually at a frequency of 2 Hz) or by tyramine 1 μmol/l and overflow from strips superfused with Ca²⁺-free solution containing K⁺ 54.7mmol/l was stimulated by introduction of Ca²⁺ 1.6mmol/l. In most of the experiments (stimulation by electrical impulses or CaCl²) neuronal and extraneuronal uptake and β-adrenoceptors were blocked by cocaine, corticosterone and propranolol, respectively. The electrically evoked overflow of ³H-labelled substances from pulmonary artery and aorta was increased by adrenocorticotropic hormone_1–24. In the pulmonary artery, the adrenocorticotropic hormone_1–24—induced increase in impulse—evoked overflow (and contraction) was the more pronounced, the lower the frequency of stimulation (6, 2 and 0.66 Hz: 360 impulses). The electrically evoked overflow of ³H-labelled substances was also increased by α-melanocyte-stimulating hormone and porcine adrenocorticotropic hormone, but was not affected by adrenocorticotropic hormone_4–10. Adrenocorticotropic hormone_1–24 also facilitated the Ca²⁺-evoked overflow of ³H-labelled substances promoted by high K⁺, but it did not affect the Ca²⁺-independent tyramine-evoked overflow. Adrenocorticotropic hormone_1–24 did not alter the percentages of [ ³H]noradrenaline and ³H-labelled metabolites contained in electrically or tyramine-evoked overflow of ³H-labelled substances.In conclusion, adrenocorticotropic hormone and fragments of adrenocorticotropic hormone cause an increase in stimulation-evoked, Ca²⁺-dependent noradrenaline release from postganglionic sympathetic nerve fibres, probably by activating presynaptic receptors for adrenocorticotropic hormone.