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

Abstract Strips of rabbit pulmonary artery and aorta were incubated with [ 3 H]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 Ca 2+ -free solution containing K + 54.7mmol/l was stimulated by introduction of Ca 2+ 1.6mmol/l. In most of the experiments (stimulation by electrical impulses or CaCl 2 ) neuronal and extraneuronal uptake and β-adrenoceptors were blocked by cocaine, corticosterone and propranolol, respectively. The electrically evoked overflow of 3 H-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 3 H-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 Ca 2+ -evoked overflow of 3 H-labelled substances promoted by high K + , but it did not affect the Ca 2+ -independent tyramine-evoked overflow. Adrenocorticotropic hormone 1–24 did not alter the percentages of [ 3 H]noradrenaline and 3 H-labelled metabolites contained in electrically or tyramine-evoked overflow of 3 H-labelled substances. In conclusion, adrenocorticotropic hormone and fragments of adrenocorticotropic hormone cause an increase in stimulation-evoked, Ca 2+ -dependent noradrenaline release from postganglionic sympathetic nerve fibres, probably by activating presynaptic receptors for adrenocorticotropic hormone.