Effects of presynaptic modulators on Ca2+-induced noradrenaline release from central noradrenergic neurons. Noradrenaline and enkephalin inhibit release by decreasing depolarization-induced Ca2+ influx.

Abstract

Slices of rat occipital cortex and hypothalamus were preincubated with 3H-noradrenaline. Tritium overflow was induced by introduction of 0.65 or 1.3 mM CaCl2 for 2–5 min after superfusion of the slices with Ca2+-free solution; Ca2+-induced overflow was promoted either by the presence of 30 mM K+ throughout superfusion or by incubation with the ionophore A 23187 (300 μM; subsequent to preincubation with 3H-noradrenaline) before onset of superfusion. The effects of drugs interfering with presynaptic α-adrenoceptors and opiate receptors on CaCl2-induced tritium overflow and on the metabolism of 3H-noradrenaline released were investigated. 1. The CaCl2-evoked tritium overflow promoted by 30 mM K+ was decreased by methionineenkephalin (1 μM). This effect was antagonized by simultaneous administration of naloxone (10 μM). When given alone, naloxone (10 μM) did not alter the CaCl2-induced overflow of tritium. 2. When cocaine (100 μM) was present in the superfusion fluid throughout the experiments, the CaCl2-evoked tritium overflow promoted by 30 mM K+ was decreased by unlabelled noradrenaline (1 μM) and increased by phentolamine (1 μM); the inhibition of CaCl2-induced tritium overflow caused by unlabelled noradrenaline was reversed by simultaneous administration of phentolamine (1 μM each). 3. The CaCl2-evoked tritium overflow promoted by ionophore A 23187 was not affected by 1 μM methionine-enkephalin or 1 μM unlabelled noradrenaline (the latter in the presence of 100 μM cocaine throughout superfusion). 4. Methionine-enkephalin, unlabelled noradrenaline and phentolamine did not significantly alter the metabolism of 3H-noradrenaline released by 1.3 mM CaCl2 under both conditions (30 mM K+ and 300 μM A 23187, respectively).