Release of [3H]noradrenaline induced by 5-hydroxytryptamine from cat pial arteries.

Pial arteries of cats were used to analyse the effects of 5-hydroxytryptamine (5-HT) on the release of [3H]noradrenaline. To achieve this the vessels were preincubated with [3H]noradrenaline and the effect of different concentrations of 5-HT (10(-6), 10(-5), 10(-4) M) on the release of tritium was studied. 5-HT elicited release of radioactivity in a dose-dependent manner. Removal of both superior cervical sympathetic ganglia 15 days before the experiment of pretreatment of the animals with reserpine (3 mg kg-1, total dose) produced a significant decrease in the outflow of tritium induced by 5-HT. In these arteries, the amount of radioactivity retained at the end of the experiment was much diminished. Cocaine (10(-6) M) caused a significant decrease in the tritium efflux induced by 5-HT (1"0(-5) M). These results show that 5-HT has an indirect adrenergic effect in the pial arteries of the cat only at high doses of 5-HT, and confirm that sympathetic innervation of these vessels mainly comes from the superior cervical ganglia.     

Noradrenergic component in the vasoconstriction induced by 5-hydroxytryptamine in goat cerebral arteries

5-Hydroxytryptamine (5-HT) elicited dose-dependent increases in tension in the middle cerebral artery of the goat, which were significantly antagonized by lysergic acid diethylamide (LSD, 10^?8 M) and methysergide (10^?7 M). In the presence of phentolamine (10^?6 M), the dose-response curve to 5-HT was shifted to the right, the pA₂ value for this antagonism was 6·52. Pretreatment of goats with reserpine (0·02 mg kg^?1 day^?1 for three days) or removal of both superior cervical ganglia 15 days before the experiment brought about a significant decrease in the vasoconstriction induced by doses of 5-HT higher than 10^?7 M. The remaining contraction produced by 5-HT in arterial segments from reserpinized or gangliectomized goats was further reduced in the presence of LSD. In addition, high concentrations of 5-HT induced tritium release from goat pial arteries preloaded with (?)-[³H]noradrenaline, 2 × 10^?7 M) which was significantly decreased in vessels from gangliectomized or reserpinized goats. These results in goat cerebral arteries indicate that in the contraction evoked by 5-HT there are two components. The first appears with low concentrations (up to 10^?7 M) in which 5-HT acts directly on 5-HT receptors. The second occurs at high doses (>10^?7 M) in which 5-HT also acts indirectly on α-adrenoceptors by release of noradrenaline from noradrenergic nerve endings.     

Mechanism of the indirect adrenergic effect of histamine in cat cerebral arteries

KCl (50 mM), tyramine (10(-7) M), and histamine (10(-4) M) induced an increase in tritium release from cat cerebral arteries preincubated with [3H]noradrenaline, this increase being due in part to noradrenaline. When calcium was absent from the superfusion medium, only tyramine (10(-7) M) enhanced the tritium outflow. Colchicine (10(-3) M) partially inhibited the increase in radioactivity brought about by 10(-4) M histamine. KCl (50 mM) also evoked release of radioactivity from cerebral arteries preloaded with [3H]histamine; this release was unaffected by reserpine pretreatment or removal of both superior cervical sympathetic ganglia. Neither tyramine (10(-7) M) nor compound 48/80 (300 micrograms ml-1) altered the spontaneous tritium outflow from cerebral blood vessels preincubated with [3H]histamine. These results suggest that histamine is not accumulated by sympathetic nerve endings and elicits its noradrenaline-releasing effect by means of an exocytotic process.     

Noradrenergic component in the vasoconstriction induced by 5-hydroxytryptamine in goat cerebral arteries

5-Hydroxytryptamine (5-HT) elicited dose-dependent increases in tension in the middle cerebral artery of the goat, which were significantly antagonized by lysergic acid diethylamide (LSD, 10(-8) M) and methysergide (10(-7) M). In the presence of phentolamine (10(-6) M), the dose-response curve to 5-HT was shifted to the right, the pA2 value for this antagonism was 6.52. Pretreatment of goats with reserpine (0.02 mg kg-1 day-1 for three days) or removal of both superior cervical ganglia 15 days before the experiment brought about a significant decrease in the vasoconstriction induced by doses of 5-HT higher than 10(-7) M. The remaining contraction produced by 5-HT in arterial segments from reserpinized or gangliectomized goats was further reduced in the presence of LSD. In addition, high concentrations of 5-HT induced tritium release from goat pial arteries preloaded with (-)-[3H]noradrenaline, 2 X 10(-7) M) which was significantly decreased in vessels from gangliectomized or reserpinized goats. These results in goat cerebral arteries indicate that in the contraction evoked by 5-HT there are two components. The first appears with low concentrations (up to 10(-7) M) in which 5-HT acts directly on 5-HT receptors. The second occurs at high doses (greater than 10(-7) M) in which 5-HT also acts indirectly on alpha-adrenoceptors by release of noradrenaline from noradrenergic nerve endings.     

Indirect adrenergic effect of histamine in human cerebral arteries: influence of post-mortem period

Histamine (10(-4) M) increased the radioactivity released from human cerebral arteries obtained within 6 h of death and preincubated with [3H]noradrenaline. In the presence of 10(-6) M cocaine or if 7 or more hours had elapsed since death, 10(-4) M histamine was unable to change basal levels of tritium outflow. The radioactivity retained by the tissue was higher when cerebral blood vessels were obtained within a post-mortem period of 6 h. These results suggest that histamine may release noradrenaline from the sympathetic innervation of human cerebral arteries and that the function of this innervation lasts only 6 h after death.     

Depolarizing responses recorded from nodose ganglion cells of the rabbit evoked by 5-hydroxytryptamine and other substances

Membrane potential changes induced by 5-hydroxytryptamine (5-HT), γ-aminobutyric acid (GABA) and 1,1-dimethyl-4-phenyl piperazinium (DMPP) were recorded from nodose ganglia (NG) by the sucrose-gap method. An amount of 0.002–0.5 μmol of the depolarizing agent was injected into the superfusion stream to the ganglion. Responses to 5-HT were also evoked from superior cervical (SCG) and dorsal root ganglia (DRG). 5-Hydroxytryptamine elicited depolarizations of graded amplitude. Maximal responses were 4.5 ± 0.4 mV in nodose ganglia compared to 2.2. ± 0.2 mV in superior cervical and 0.6 ± 0.1 mV in dorsal root ganglia (means ± SEM). In nodose ganglia, GABA induced smaller maximal depolarizations than did 5-HT, similar to those evoked by DMPP; dopamine was a weak depolarizing agent while substance P was apparently inactive.The dose-response curve for 5-HT in nodose ganglia was parallel to that for 5-HT in superior cervical ganglia and significantly to the left (ED₅₀ values 0.029 and 0.098 μmol). Curves for 5-HT and GABA in nodose ganglia were superimposable. The high sensitivity of nodose ganglia cells to 5-HT is briefly discussed. Analogues of 5-HT lacking a hydroxyl group at position 5 on the nucleus were relatively inactive as depolarizing agents.Picrotoxin (10^?6 ? 10^?5 M) reduced or suppressed responses in nodose ganglia to GABA, whereas responses to 5-HT and DMPP were not much affected or, in the case of 5-HT, sometimes somewhat reduced. Quipazine (10^?6 M) was a selective antagonist of 5-HT responses in nodose ganglia; those to GABA and DMPP were not significantly altered. Neither trazodone nor LSD displayed antagonist properties at 5-HT receptors in nodose ganglia.     

Indirect adrenergic effect of histamine in cat cerebral arteries

Summary Histamine (10(^–4 M) induced an increase in the tritium outflow from cat cerebral arteries preloaded with ³H-noradrenaline. Pretreatment with reserpine (3 mg/kg, i.p., total dose) or removal of both superior cervical ganglia two weeks before the experiment abolished that increase. The presence of cocaine or diphenhydramine also prevented the rise in tritium efflux induced by histamine.Histamine (10(^–8 M to 10(^–3 M) elicited dose-dependent contractions in the isolated posterior communicating artery of the cat which were reduced in the presence of diphenhydramine at all doses except the highest three. The addition of phentolamine to the bath decreased the contractile responses at the doses lower than 10(^–6 M. Pretreatment with reserpine or removal of both superior cervical ganglia also diminished the responses at doses of histamine below 10(^–6 M and 10(^–5 M, respectively. When cocaine was added to the bath there was a decrease in the contraction elicited at all doses except the last one.These results suggest the existence of an indirect adrenergic mechanism in the contractile response to histamine in cat cerebral arteries.     

Effect of pentobarbital on the noradrenaline release induced by drugs and field electrical stimulation from cerebral and femoral arteries of the cat

The present studies showed that field electrical stimulation, high potassium (K⁺), tyramine and ionophore X537A induced tritium release from cerebral and femoral arteries of cat prelabelled with [³H]noradrenaline. The secretion caused by K⁺ or field stimulation was Ca²⁺-dependent and was antagonized by high concentrations of pentobarbital (10^?4 and 10^?3M), whereas that induced by the rest of the drugs was unchanged in the same situations. The noradrenaline uptake by these arteries was reduced by pentobarbital (10^?3M and 10^?4M). These results suggest that this barbiturate interferes with Ca²⁺ entry to the adrenergic nerve endings, and therefore antagonizes the noradrenaline release by Ca²⁺-dependent processes (exocytosis).     

Diet-induced atherosclerosis inhibits release of noradrenaline from sympathetic nerves in rabbit arteries

Contractile responses to sympathetic nerve stimulation and exogenous noradrenaline were compared in aortas and pulmonary arteries of control rabbits and rabbits fed a cholesterol-rich diet (0.3%) for 16 or 30 weeks. The diet-induced atherosclerosis reduced the contractions to increasing concentrations of exogenous noradrenaline (0.1 nM to 10 μM) in both arteries, and the reduction was more pronounced after 30 weeks of the hypercholesterolemia. The contractions produced with increasing frequencies of electrical stimulation (1–32 Hz) were nearly abolished in the atherosclerotic arteries. Labeling of the aorta and the pulmonary arteries with [³H]noradrenaline resulted in accumulation of radioactivity in both control and atherosclerotic blood vessels. After mounting the labeled blood vessels for superfusion, a basal efflux of [³H]noradrenaline and of ³H-metabolites was detected. In the atherosclerotic arteries, a decreased efflux of the intraneuronal deaminated metabolites 3,4-dihydroxyphenyl glycol (DOPEG) and 3,4-dihydroxymandelic acid (DOMA) was detected. Electrical stimulation at 1 Hz (pulmonary artery) or 2 Hz (aorta) caused an augmented efflux of total ³H from the control arteries; this was mostly due to release of intact [³H]noradrenaline. The electrical imp ulses evoked significantly less (16 weeks) or no (30 weeks) release of [³H]noradrenaline in the atherosclerotic arteries. These data illustrate that diet-induced atherosclerosis exerts an inhibitory action on the sympathetic nerve terminals in the aorta and the pulmonary artery of the rabbit. This effect, together with an inhibitory effect at the postjunctional level results in a loss of the responsiveness to nerve stimulation. The atherosclerotic process also inhibits the intraneuronal deamination of the sympathetic transmitter.     

Analysis of the contractile effect of 5-hydroxytryptamine on the isolated posterior communicating artery of the cat

5-Hydroxytryptamine (5-HT) induced dose-dependent increases in tension on the isolated posterior communicating artery (PCA) of the cat were significantly antagonized by lysergic acid diethylamide (LSD, 6 times 10^?9 m). In the presence of phentolamine (10^?6 m) the contraction induced by the two lowest doses of 5-HT was significantly reduced. Pretreatment of the animals with reserpine (3 mg kg^?1, i.p., total dose) did not modify the dose-response curve to 5-HT except for the lowest dose. Removal of both superior cervical sympathetic ganglia 15 days before the experiment brought about a significant increase in the vasoconstriction induced by 5-HT at all the doses compared with the control. Cocaine (10^?6m) induced a significant shift to the left of the dose-response curve to 5-HT but the maximum response was the same as in the control. The augmented response to 5-HT after denervation was partially antagonized by LSD (6 times 10^?9 m) but not by phentolamine (10^?6 m). These results show that the vasoconstriction elicited by 5-HT in the PCA of the cat is mainly due to direct stimulation of tryptaminergic receptors. The participation of an indirect adrenergic component in the contractile effects of 5-HT seems to be negligible.     

MODULATION OF ENDOGENOUS NORADRENALINE RELEASE BY PREJUNCTIONAL α-ADRENORECEPTORS: COMPARISON OF A CEREBRAL AND PERIPHERAL ARTERY

• 1 Stimulation-evoked fractional release/pulse of noradrenaline (NA) is markedly different in the rabbit basilar artery as compared to the rabbit ear artery. Therefore, using both agonists and antagonists of prejunctional α-adrenoreceptors, the hypothesis that there are differences in prejunctional mechanisms between these functionally different arteries was tested.
• 2 Clonidine (10^?6M) had similar effects on NA release in both vessels, decreasing release at 2 Hz, but increasing release at 8 Hz. However, 10^?5M clonidine had different effects in the two vessels.
• 3 α-Adrenoreceptor antagonists, phentolamine (10^?6M), yohimbine (10^?5M), and phenoxybenzamine (10^?5M), all increased NA release to a similar extent in both vessels. However, the effect of phenoxybenzamine was considerably greater than that of the other two antagonists, suggesting that it may have additional sites of action.
• 4 When the effects of modest drug concentrations were considered, no major qualitative or quantitative differences in the effects of agonists and antagonists on NA release from the two vessels were seen. Thus, the difference in fractional NA release between the basilar and ear arteries cannot be accounted for by differences in prejunctional α-adrenoreceptor modulation.

     

A pre-junctional action of 5-hydroxytryptamine and methysergide on noradrenergic nerves in dog isolated saphenous vein

Electrical stimulation (2 Hz for 2 min) of dog isolated saphenous vein strips pre-incubated with tritiated noradrenaline increased the overflow of tritium of which about 80% was noradrenaline. 5-Hydroxytryptamine (5-HT; 1·0 × 10^?9-1·0 × 10^?7 mol litre^?1) and methysergide (3·0 × 10^?8-3·0 × 10^?8 mol litre^?1) inhibited the induced overflow of total tritium by a maximum of 78 ± 4% and 47 ± 7% respectively (mean ± s.e. mean, n = 6 for each). Methysergide was about 30 times less potent than 5-HT and the maximum inhibition obtained was less than with 5-HT. Both compounds inhibited electrically-induced contractions and overflow of tritiated noradrenaline. Their inhibitory actions on tritium overflow were little affected by phentolamine (1·0 × 10^?8 mol litre^?1) or cyproheptadine (1·0 × 10^?8 mol litre^?1), nor was the inhibitory effect of methysergide on electrically induced contractions antagonized by atropine, mepyramine, cimetidine or propranolol. The findings suggest that the prejunctional inhibitory effect of methysergide may be mediated via stimulation of a 5-HT receptor which, unlike the D-receptor, is not blocked by cyproheptadine. The possibility that the pre-junctional 5-HT receptor in the dog saphenous vein is the same as the post-junctional receptor in this preparation is discussed.     

Influence of calcium on noradrenaline release evoked by 5-hydroxytryptamine,tyramine and potassium from goat pial arteries

The release of tritium (³ H) evoked by tyramine, potassium (K⁺) and 5-hydroxytryptamine (5-HT) from goat pial arteries preloaded with [³ H]noradrenaline (³ H-NA) was studied. In normal Krebs-bicarbonate solution (KBS) all these agents caused a transient increase in radioactivity release over the basal spontaneous outflow. The pattern of release evoked by 5-HT was similar to that induced by tyramine with a slow onset and decline, but different from that induced by K⁺ which produced a rapid peak of ³ H release followed by a quick fall. The removal of Ca²⁺ from the medium did not modify the efflux of radioactivity caused by tyramine, but the ³ H efflux produced by K⁺ was markedly reduced. Nevertheless, in this Ca²⁺ -free medium the ³ H release evoked by 5-HT was partially, but significantly, decreased. These results indicate that K⁺ evokes NA release by a Ca²⁺ -dependent process, probably of an exocytotic nature, while tyramine mediates NA release by means of a Ca²⁺ -independent mechanism. However, 5-HT possesses a Ca²⁺ -dependent and a tyramine-like component.     

Inhibition of adrenergic neurotransmission by prostaglandin E1 (PGE1) in the rabbit ear artery.

Isolated central ear arteries of rabbits were perfused with Krebs solution at a constant flow rate of 2–7 ml/min. Pressure changes to periarterial nerve stimulation (1, 3, 10 and 30 Hz; 5–32 pulses) and to noradrenaline were measured in the presence and absence of prostaglandin E₁ (PGE₁). This substance in concentrations of 7 × 10^?9– 4.5 × 10^?7 produced a dose-dependent inhibition of constrictor responses to nerve stimulation. The degree of inhibitory action of PGE₁ became progressively less as the frequency or length of stimulation was increased. Prostaglandin E₁ (1.1 × 10^?7 M) failed to affect the constrictor responses to noradrenaline and it markedly reduced the stimulation-evoked release of radioactivity from arteries incubated with [³]noradrenaline. The results indicate that PGE₁ inhibits the vasoconstrictor responses of rabbit ear artery to nerve stimulation by reducing the release of the adrenergic transmitter.     

Interference of pentobarbitone with the contraction of vascular smooth muscle in goat middle cerebral artery

Pentobarbitone (10^?5 to 10^?3 M) decreased the basal tone of vascular smooth muscle of goat middle cerebral artery in a dose-dependent manner as well as relaxing established contractions induced by noradrenaline (NA) (10^?5 M), 5-hydroxytryptamine (5-HT) (10^?5 M) and KCl(120 mM). Preincubations with pentobarbitone reduced the contractions evoked by these three agents in a dose-dependent way. It also decreased Ca²⁺-induced contractile responses in K⁺-depolarized arteries and 5-HT-Ca²⁺ and NA-Ca²⁺ contractions dose-dependently. Contractions induced by K⁺ were more sensitive to the depressant actions of the drug than those produced by NA and 5-HT. The small contractions evoked by K⁺ and 5-HT in Ca²⁺-free medium were also reduced in its presence. The antagonism Ca²⁺-pentobarbitone was insurmountable. These results suggest that the drug interferes with Ca²⁺ entry and Ca²⁺ release from cell stores, and therefore with the smooth muscle contractions.     

The in vitro uptake of biogenic amines by snail (Heliz pomatia) nervous tissue.

The uptake of [³H]5-HT, [³H]dopamine, [³H]noradrenaline and [³H]octopamine into the suboesophageal ganglia of the snail, Helix pomatia, was studied. When tissues were incubated at 25° in mediums containing radioactive amines, tissue: medium ratios of about 30:1, 18: l, 4:1 and 5:1 for 5-HT, dopamine, noradrenaline and octopamine respectively were obtained after 20–30 min incubation. Tissues incubated at 25° in mediums containing radioactive amines for 20–30 min showed that 90% of the radioactivity was present as unchanged [³H]5-HT, [³H]dopamine, [³H]noradrenaline or [³H]octopamine. The high tissue : medium ratios for 5-HT and dopamine, but not for noradrenaline and octopamine, demonstrated saturation kinetics which were dependent upon temperature and sodium ions. From the Lineweaver-Burk plots, two uptake mechanisms for 5-HT at 25° were resolved, the high affinity uptake process having a K_m1valueof 8.48 × 10^?8 M and V_max1 value of 0.077 nmole/g per min, while the lower affinity process had a K_m2 value of 1.8 × 10^?6 M and a V_max2 value of 0.66 mole/g per min. At 0° a single uptake mechanism for 5-HT occurred which gave a K_m value of 0.152 × 10^?8 M and a V_m value of 0.0203 nmole/g per min. In the case of dopamine, the Lineweaver-Burk plot of 25° showed a single uptake process with values for K_m and V_max of 1.02 × 10^?7 M and 0.0673 nmole/g per min respectively. This process did not function at 0°. The effects of various agents and ions upon the accumulation processes for all amines were also studied, and the findings indicate that the same neurons may well accumulate more than one amine type. It is concluded that 5-HT and dopamine uptake in the snail ganglia is a mechanism for inactivating these substances at 25° and that an uptake mechanism for 5-HT also functions at 0°. The present results are discussed from the point of view of the monoamines having transmitter functions in the snail CNS.     

Calcium Channels Involved in Noradrenaline Release from Sympathetic Neurones in Rabbit Carotid Artery*

Abstract: Transmitter release from nerve terminals is dependent on the entry of Ca²⁺ through neuronal voltage‐gated calcium channels. In sympathetic neurones both N‐ and L‐type calcium channels are present. Potassium channel blockade increases Ca²⁺ entry into sympathetic neurones. We examined the participation of N‐ and L‐type calcium channels in the stimulation‐evoked release of noradrenaline from vascular sympathetic neurones. Rings of rabbit carotid artery were preincubated with [³H]‐noradrenaline. Electrical field stimulation was used to evoke ³H overflow. The selective N‐type calcium channel blocking agent ω‐conotoxin GVIA (single concentrations: 3×10^?10–10^?8 M) caused a slowly developing reduction of the stimulation‐evoked ³H overflow. At 3×10^?8 M, ω‐conotoxin GVIA caused an equilibrium block with a rapid (15 min.) onset. After 2 hr exposure to ω‐conotoxin the inhibition was steady (pIC₅₀ (‐log M): 9.43; E_max: 91%). The selective L‐type calcium blocking agents nifedipine (10^?7–10^?5 M) and nimodipine (10^?8–10^?5 M) had no effect on the stimulation‐evoked ³H overflow. The calcium channel opener Bay K 8644 (10^?6 M) likewise had no effect. The potassium channel blocking agent 4‐aminopyridine (10^?5–10^?3 M) enhanced the stimulation‐evoked ³H overflow up to 5 times. 4‐Aminopyridine (10^?4 M) did not alter the inhibitory effect of ω‐conotoxin GVIA (3×10^?8 M). In the presence of 4‐aminopyridine (10^?4 M), nifedipine (10^?5 M) and nimodipine (10^?6 M) enhanced the ³H overflow. We conclude that the stimulation‐evoked release of noradrenaline from sympathetic neurones in rabbit carotid artery is mediated by N‐type calcium channels and that L‐type channels are not involved even when potassium channels are blocked by 4‐aminopyridine.     

Effects of prostaglandin E1 and indomethacin on the stimulation- evoked overflow of 3H-noradrenaline from guinea-pig taenia caecum

Prostaglandin E₁ (5.8 × 10^?8 M) markedly and reversibly reduced the stimulation-evoked overflow of total tritium, while it had no effects on basal outflow. Indomethacin (8.4 × 10^?6 M) increased the stimulation-evoked overflow of total tritium at low frequencies (2–5 Hz), while it had no effect at high frequencies of stimulation (more than 10 Hz). It was concluded that endogenous prostaglandin E₁ also plays a regulatory role in adrenergic inhibitory neurotransmission by inhibiting the noradrenaline release from adrenergic nerve terminals of the guinea-pig taenia caecum.     

No evidence for reverse trans-synaptic regulation of neuronal uptake by beta-adrenoceptors in kitten atria

Kitten atria incubated with [³H]noradrenaline, 1.18 × 10^?7 M for 10 min or 3 × 10^?9 M for 30 min, actively accumulated the amine. Final tissue tritium concentrations were 2–4-fold and 8–12-fold higher, respectively, than those of the incubation fluid. Uptake was consistently greater in right than in left atria. The β₁-adrenoceptor antagonist, practolol, 10^?6 or 10^?5 M, and the β₁- and β₂-adrenoceptor antagonist, propranolol, 5 × 10^?8, 5 × 10^?7or 5 × 10^?6 M, did not affect noradrenaline uptake. Reverse trans-synaptic regulation of neuronal noradrenaline uptake by β-adrenoceptors therefore does not appear to operate in kitten atria as has been reported for rat atria and other tissues.     

Involvement of alpha-receptors in clonidine-induced inhibition of transmitter release from central monoamine neurones

Slices of rat cerebral cortex preincubated with (?)-³H-noradrenaline or ³H-5-hydroxytryptamine were stimulated by an electrical field, and the stimulation-induced overflow of tritium was determined. (1) Clonidine diminished the stimulation-evoked tritium overflow from slices preincubated with ³H-noradrenaline. The degree of this inhibition was greater at a low than at a high frequency of stimulation. (2) A high concentration of clonidine (10^?5 M) did not antagonize the increase of the stimulation-induced overflow caused by 10^?6 M or 10^?5 M cocaine, but abolished the increase caused by 10^?7 M of phentolamine or phenoxybenzamine. In the presence of cocaine, the inhibitory effect of clonidine was reduced. (3) 10^?5 M clonidine diminished the stimulation-evoked overflow of tritium from slices preincubated with ³H-5-hydroxytryptamine. (4) It is concluded that clonidine decreases, and phentolamine and phenoxybenzamine increase, the stimulation-induced release of noradrenaline from cerebral neurones by an activation and a blockade of α-receptors, respectively. A variety of secretory cells (secreting catecholamines, acetylcholine, 5-hydroxytryptamine, insulin or renin) seem to be endowed with structures similar to α-adrenergic receptors, which can modulate the secretion process.