Role of cAMP for regulation of impulse-evoked noradrenaline release from the rabbit pulmonary artery and its possible relationship to presynaptic ACTH receptors.

Strips of the rabbit pulmonary artery preincubated with 3H-noradrenaline were superfused with physiological salt solution containing cocaine, corticosterone and propranolol. Basal tritium efflux and electrically evoked tritium overflow were determined. The basal efflux of tritium was not affected by forskolin 0.01-10 mumol/l, 8-Br-cAMP and dibutyryl-cAMP 10-330 mumol/l, or the phosphodiesterase inhibitors rolipram 1-10 mumol/l and AH 21-132 l mumol/l; it was increased by AH 21-132 10-100 mumol/l. Forskolin concentration-dependently increased the evoked 3H overflow, and this effect was not attenuated by omission of cocaine. The facilitatory effect of forskolin was more pronounced at 0.66 Hz than at 2 Hz. Rolipram, AH 21-132, 8-Br-cAMP or dibutyryl-cAMP also produced a concentration-dependent increase in evoked 3H overflow (8-Br-cAMP was more effective than dibutyryl-cAMP in this respect). Except for the highest concentration investigated, AH 21-132 was more effective in facilitating evoked overflow than in increasing basal efflux. Forskolin, AH 21-132 or 8-Br-cAMP did not alter the percentages of 3H-noradrenaline and 3H-metabolites contained in basal tritium efflux or in stimulation-evoked tritium overflow. When a combination of AH 21-132 plus 8-Br-cAMP or AH 21-132 plus forskolin was administered, the facilitatory effect on evoked tritium overflow was more pronounced than with the single compounds alone. ACTH1-24 also facilitated the evoked tritium overflow. Combined exposure to ACTH1-24 plus forskolin, ACTH1-24 plus AH 21-132 or ACTH1-24 plus forskolin plus AH 21-132 resulted in a clearly more pronounced increase in evoked tritium overflow than exposure to the single compounds alone.(ABSTRACT TRUNCATED AT 250 WORDS)