Jan Abrahamsen

Presynaptic action of adrenaline on adrenoceptors modulating stimulation-evoked 3H-noradrenaline release from rabbit isolated aorta

SummaryThe purpose of this investigation was to study the effect of adrenaline on presynaptic adrenoceptors by recording the release of 3H-noradrenaline evoked by electrical-field stimulation. Adrenaline (10−10−3 × 10−9 mol/l) had no effect on the 3H-overflow evoked by stimulation of aorta preloaded with 3H-noradrenaline. At 10−8 and 3 × 10−8 mol/l, the 3H-overflow was decreased by up to 47%. The maximum decrease was more marked in the presence of either cocaine (3 × 10−5 mol/l) plus corticosterone (4 × 10−5 mol/l), cocaine (3.3 × 10−6 mol/l) plus normetanephrine (4 × 10−5 mol/l), or desipramine (10−6 mol/l) plus normetanephrine (10−5 mol/l). The relationship between adrenaline-induced decrease and stimulation-frequency was dependent on the experimental design: either the decrease was the same at all frequencies (1–16 Hz) or it was more marked, the lower the frequency (1 > 3 > 8 Hz). Phentolamine and rauwolscine (both 10−6 mol/l) antagonized the inhibitory effect of adrenaline (10 − 8−10−6 mol/l). Phenoxybenzamine (10−6 mol/l), prevented the inhibitory effect. No enhancing effect of adrenaline (10−9−10−6 mol/l) was observed in the presence of these three α-adrenoceptor antagonists. Our results suggest that adrenaline activates inhibitory α2-adrenoceptors, but not facilitatory β-adrenoceptors on postganglionic sympathetic nerve terminals in rabbit aorta.

Lack of presynaptic modulation by isoprenaline of 3H-noradrenaline release from rabbit isolated ear artery

SummaryThe aim of the present investigation was to examine whether or not presynaptic facilitatory β-adrenoceptors are detectable on the postganglionic nerves in the rabbit isolated ear artery. Strips of rabbit central ear artery were incubated with 3H-noradrenaline (10−7 mol/l; 30 min or 10−6 mol/l; 60 min). Subsequently, they were washed repeatedly with physiological salt solution. The strips were subjected to electrical-field stimulation (S1–S8) and the resultant 3H-overflow was determined.When the ear artery was stimulated with 150 pulses (0.5 ms; 3 Hz; 225 mA), isoprenaline (10−9−10−6 mol/l) either alone or in the presence of either rauwolscine (10−6 mol/l) or phentolamine (10−6 mol/l) did not alter the stimulation-evoked 3H-overflow. This was also the case in the presence of rauwolscine (10−6 mol/l) plus either the selective phosphodiesterase inhibitor ICI 63 197 (3 × 10−5 mol/l) or forskolin (10−6 mol/l). When the ear artery was stimulated with 300 pulses (1 ms; 5 Hz; 225 mA), isoprenaline had no effect on the stimulation-evoked 3H-overflow. This was also the case when phentolamine (10−6 mol/l) was present. Propranolol (10−7−10−5 mol/l) did not alter the stimulation-evoked 3H-overflow. In some experiments, the stimulation current was reduced to 175 mA in order to obtain similar reference release (S3) values despite the presence of rauwolscine (150 pulses; 0.5 ms; 3 Hz). Even then, isoprenaline (10−9−10−6 mol/l) did not change stimulation-evoked 3H-overflow. The results suggest that postganglionic sympathetic nerves in rabbit central ear artery do not possess presynaptic facilitatory β-adrenoceptors.

Presynaptic Modulation by Adrenaline of 3H-Noradrenaline Release in Rabbit Ear Artery

The aim of the present investigation was to examine the ability of adrenaline to modulate presynaptically the stimulation-evoked release of noradrenaline from postganglionic sympathetic nerves in the rabbit ear artery. Strips of rabbit central ear artery were incubated with 3H-noradrenaline. Subsequently, they were washed repeatedly with physiological salt solution containing cocaine and corticosterone. The strips were subjected to repeated electrical-field stimulation (S1-S8, 150 pulses, 0.5 ms, 225 mA, 3 Hz) and the resultant 3H overflow was determined. Adrenaline (10(-8) to 10(-6) mol/l) and clonidine (10(-9) to 10(-6) mol/l) reduced the stimulation-evoked 3H overflow. Rauwolscine (10(-7) to 10(-5) mol/l) and phentolamine (3 x 10(-7) to 3 x 10(-5) mol/l) enhanced markedly the stimulation-evoked 3H overflow. Rauwolscine (10(-6) mol/l) abolished the inhibitory effect of low concentrations of adrenaline (10(-8) to 10(-7) mol/l) and clonidine (10(-9) to 10(-7) mol/l) and attenuated the inhibitory effect of the highest concentration (10(-6) mol/l) of clonidine, but not that of adrenaline. In some experiments, the stimulation current was reduced to 175 mA in order to obtain similar reference release (S3) values despite the presence of rauwolscine. Even then, only the highest concentration (10(-6) mol/l) of adrenaline decreased the stimulation-evoked 3H overflow. Facilitation was not seen. It is concluded that adrenaline activates inhibitory presynaptic alpha 2-adrenoceptors. Furthermore, adrenaline does not reveal the presence of presynaptic facilitatory beta-adrenoceptors in the rabbit ear artery.