Modification of the evoked release of noradrenaline from the perfused cat spleen by various ions and agents

1 The effect of tetraethylammonium (TEA) and 4-aminopyridine (4-AP) on the inhibitory effect of guanethidine on noradrenaline (NA) release was investigated in the perfused spleen of the cat. 2 Guanethidine blocked the release of NA evoked by nerve stimulation. TEA and 4-AP readily reversed this inhibitory effect, and the NA output was nearly doubled after repeated stimulation of the nerves. On subsequent perfusion with Krebs solution without TEA or 4-AP, the inhibitory effect of guanethidine reappeared. 3 The reversal of guanethidine blockade of sympathetic nerves by TEA and 4-AP is discussed.

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Reversal of Guanethidine Blockade of Sympathetic Nerve Terminals by Tetraethylammonium and 4‐aminopyridine

Kirpekar

Prat

1978

“…In a recent paper (Kirpekar et al, 1983) we observed that La3+ and Mn+ inhibited the release of tritium evoked by TEA; however, in the s present paper high Mg2" did not affect the secretory responses to TEA or 4-AP (Figure 4). This was a paradoxical finding since it is well known that Mg2", f La3+ and Mn2" behave as inorganic Ca2" antagonists I that inhibit equally noradrenaline release evoked by depolarizing stimuli (Kirpekar & Misu, 1967;Kirpekar & Wakade, 1968;Kirpekar et al, 1972). Because La3" and Mn2+ precipitate out in HC03--containing solutions, we always used Tris (5 mM) to buffer solutions containing those cations and eliminated from them the anions HCO3 and H2PO4 .…”

Section: Discussionmentioning

confidence: 99%

“…Tetraethylammonium (TEA) and 4-aminopyridine (4-AP) increase the amounts of noradrenaline released upon electrical stimulation of sympathetic nerves (Thoenen et al, 1967;Kirpekar et al, 1972;Wakade, 1980). The TEA ion and 4-AP are known to block selectively the delayed outward K+ current responsible for repolarization, thereby prolonging the duration of the action potential in several neuronal types (Thesleff, 1980); this situation allows Ca2+ channels to open longer and more Ca2+ to enter the nerve terminal to evoke an increased transmitter release.…”

Section: Introductionmentioning

confidence: 99%

Ion dependence of the release of noradrenaline by tetraethylammonium and 4‐aminopyridine from cat splenic slices

Ceña¹,

Garcı́a

González-García³

et al. 1985

1 Cat splenic slices prelabelled with [3H]-noradrenaline were incubated in oxygenated Krebsbicarbonate solution at 37°C, and the spontaneous total 3H release into different incubation media monitored. In normal Krebs bicarbonate solution, the spontaneous tritium fractional release amounted to 3.7% of the tissue radiactivity content per 5 min collection period. 2 Tetraethylammonium (TEA) increased spontaneous transmitter release in a concentrationdependent manner; the release was maximal at 30 mM and was 3.5 times the basal release. 3 4-Aminopyridine (4-AP) also enhanced the spontaneous release of tritium. The response increased linearly with 4-AP concentration (1-10 mM). With 10 mM 4-AP, the release was as much as 6 times the basal transmitter release. Guanidine was much less potent than either TEA or 4-AP. 4 The secretory response to TEA or 4-AP was little affected by changes in external Ca2", Mg2+, Na+, Cl-, H2PO4 or by tetrodotoxin. 5 However, transmitter release evoked by TEA or 4-AP strongly depended upon the concentration of HCO3-of the incubation solution; in fact, the secretory response varied almost linearly between I and 25 mM HCO3 . 6 The mechanisms underlying these effects are probably related to the well-known ability ofTEA and 4-AP to block K+ conductance that would cause depolarization of the splenic sympathetic nerve terminals. The HCO3-requirements for the secretory response are probably related to the ability of C02/HCO3-solutions to mobilize and release Ca2+ from intracellular organelles.

“…Evidently, TEA and rubidium ions also prolong the nerve action potential (Koketsu, 1958;Baker, Hodgkin & Shaw, 1962), and their enhancing effect on evoked NA release may likewise be explained in terms of an action on calcium influx. Kirpekar et al (1972) have, as an alternative, explained enhanced NA release by TEA and rubidium as a result of their capacity to inactivate potassium channels (cf. Katz & Miledi, 1969), assuming that the outward movement of potassium during the nerve action potential controls the release of NA by modulating the calcium entry into the axon.…”

Section: Introductionmentioning

confidence: 99%

Further Evidence That Prostaglandins Inhibit the Release of Noradrenaline From Adrenergic Nerve Terminals by Restriction of Availability of Calcium

Hedqvist

1976

I Guinea-pig vasa deferentia were continuously superfused after labelling the transmitter stores with P3HI-(-)-noradrenaline. Release of [3H1-(-)-noradrenaline was induced by transmural nerve stimulation. 2 Prostaglandin E2 (14 nM) drastically reduced the release of [3H]-(-)-noradrenaline, while tetraethylammonium (2 mM), rubidium (6 mM), phenoxybenzamine (3 giM) each in the presence or absence of Uptake 1 or 2 blockade, and prolonged pulse duration (from 0.5 to 2.0 ms) all significantly increased the release of PHI4--noradrenaline per nerve impulse. 3 The inhibitory effect of prostaglandin E2 on evoked release of [3HI-(-)-noradrenaline was significantly reduced by tetraethylammonium, rubidium and prolonged pulse duration, whilst it was actually enhanced by phenoxybenzamine. This indicates that increased release of noradrenaline per nerve impulse does not per se counteract the inhibitory effect of prostaglandin E2. 4 It is concluded that tetraethylammonium, rubidium and prolonged pulse duration counteracted the inhibitory effect of prostaglandin E2 on 13HI-(-)-noradrenaline release by promoting calcium influx during the nerve action potential. The results are consistent with, and add more weight to the view that prostaglandins inhibit the release of noradrenaline by restriction of calcium availability.