Effect of Guanidine on Release of Noradrenaline From the Perfused Spleen of the Cat

Abstract

1 Guanidine increased noradrenaline (NA) output at 5 Hz by 3 to 6 fold, and doubled it at 30 Hz. Onset of maximum activity was slow, and reversal was also slow. Output of NA induced by potassium, sodium deprivation, or tyramine was not affected. 2 NA output was doubled at low concentrations (1 to 2 mM) of guanidine, but maximal effect was obtained at 4 mM. At 10 mM, spontaneous release was occasionally observed. 3 The effect of guanidine on NA release was related to the external calcium concentration. Outputs which previously have been shown to be insignificant at 5 Hz in 0.25 and 0.75 mm calcium-Krebs solution were markedly enhanced by guanidine. Guanidine enhanced release at all calcium concentrations up to 7.5 mm, but maximum output was obtained at 2.5 mm. 4 Guanidine had no effect on the recovery of intra-arterially infused NA. 5 The effects of guanidine and tetraethyl-ammonium (TEA) on NA release at 5 Hz were additive. 6 Guanidine reversed the inhibition of NA release by guanethidine during nerve stimulation at 5 and 10 Hz, and the NA output increased nearly 2.5 fold after repeated stimulation of the nerves. Guanidine was less effective in reversing the inhibitory effects of guanethidine on NA release at 30 Hz. 7 Guanidine did not affect release of catecholamines (CA) from the perfused cat adrenal gland by splanchnic nerve stimulation. 8 It is suggested that guanidine enhances NA release partly by increasing the influx of calcium into the neurone during an action potential, and also by interfering with intracellular binding ot calcium.

EFFECTS OF AMILORIDE ON CONTRACTIONS AND THE RELEASE OF TRITIUM FROM RAT VAS DEFERENS PRELOADED WITH [3H]‐NORADRENALINE

“…This suggestion is in accordance with the observation that amiloride inhibits the entry of sodium ions into other cells (Bentley, 1968;Nagel & Dorge, 1970;Gatzy, 1971;Aceves & Cereijido, 1973). It is interesting that guanidine increases the release of noradrenaline induced by electric nerve stimulation without affecting the release induced by KCl (Hirsch, Kirpekar & Prat, 1979). It is possible that guanidine increases the permeability of sodium channels, while its derivatives (amiloride and tetrodotoxin) block the sodium channel.…”

New Considerations on the Neuromodulatory Role of Thiamine

“…pyrithiamine, guanidine) may enhance calcium-mediated neurosecretion of some neurotransmitters, but only when the initial stimulus is intermittent (e.g. electric field stimulation) and not when the process is experimentally evoked by high potassium [17,25] .…”