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 mumol/l and overflow from strips superfused with Ca2+-free solution containing K+ 54.7 mmol/l was stimulated by introduction of Ca2+ 1.6 mmol/l. In most of the experiments (stimulation by electrical impulses or CaCl2) neuronal and extraneuronal uptake and beta-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. In the pulmonary artery, the adrenocorticotropic hormone--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 alpha-melanocyte-stimulating hormone and porcine adrenocorticotropic hormone, but was not affected by adrenocorticotropic hormone. Adrenocorticotropic hormone 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 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.