P. Alberts

Site(s) and ionic basis of α‐autoinhibition and facilitation of [3H]noradrenaline secretion in guinea‐pig vas deferens

1. Mechanisms controlling the secretion of [3H]noradrenaline from the noradrenergic nerves of guinea‐pig isolated vas deferens, prelabelled by incubation with [3H]noradrenaline, were studied using (a) different modes of (extramural or transmural) electrical nerve stimulation (a total of 300 shocks of varying strength, and a duration of 2 msec) at 1‐30 Hz, or (b) depolarizing concentrations of K+ (60‐110 m m).

The effects of atropine on [3H]acetylcholine secretion from guinea-pig myenteric plexus evoked electrically or by high potassium

1. The myenteric plexus‐longitudinal muscle preparation of the guinea‐pig ileum was incubated with [3H]choline (1·125‐1·5 μM), and then superfused with Tyrode solution containing hemicholinium‐3 (10 μM). Secretion of [3H]acetylcholine ([3H]ACh) was evoked either (a) by electrical field stimulation (0·5‐15 Hz, 150 shocks per period, 0·5 msec), used to ‘indirectly’ depolarize the varicosities of nerve terminals, or (b) by high potassium (40 mM with 1 μM‐tetrodotoxin, for 6 min, or 80 mM without tetrodotoxin, for 1 min), to ‘directly’ depolarize varicosities.

The influence of 8-Br 3′,5′-cyclic nucleotide analogs and of inhibitors of 3′,5′-cyclic nucleotide phosphodiesterase, on noradrenaline secretion and neuromuscular transmission in guinea-pig vas deferens

SummaryThe effects of 3′,5′-cyclic nucleotide phosphodiesterase (PDE) inhibitors and of 8-Br 3′,5′-cyclic nucleotide analogs on nerve-muscle transmission were studied in the guinea-pig vas deferens preincubated with 3H-noradrenaline.8-Br cyclic AMP and the PDE inhibitors 3-isobutyl-1-methylxanthine (IBMX) and 3-propionyl-4-hydrazinopyrazolopyridine (SQ 20006) enhanced the secretion of 3H-NA evoked by transmural nerve stimulation. 8-Br cyclic GMP was without effect in this respect.The muscle contraction evoked by transmural nerve stimulation, high potassium or by application of exogenous noradrenaline was depressed by IBMX and SQ 20006. The contraction evoked by transmural nerve stimulation was enhanced by 8-Br cyclic AMP and depressed by 8-Br cyclic GMP.These findings suggest differential involvement of 3′,5′-adenosine- and guanosine-cyclic nucleotides in excitation-secretion-coupling in the noradrenergic sympathetic nerves, and in excitation-contraction-coupling in the smooth muscle, of guinea-pig vas deferens.

Acetylarsenocholine: A Cholinergic Agonist

Abstract: The pharmacological properties of acetylarsenocholine, an arsenic analogue of acetylcholine, were investigated. Acetylarsenocholine behaved as a cholinergic ligand both in the central and peripheral nervous system. It bound to nicotinic receptors in rat medulla‐pons with a KD of 15 μM and to muscarinic receptors in rat cerebral cortex with a KD of 10 μM. It behaved also as an agonist at presynaptic muscarinic receptors in guinea pig ileum myenteric plexus preparation. Arsenocholine is an alternative substrate for choline acetyltransferase and acetylarsenocholine is an alternative substrate for acetylcholinesterase.

IS THE ALPHA-ADRENOCEPTOR MEDIATED INHIBITION OF NORADRENALINE SECRETION A NEGATIVE FEEDBACK CONTROL IN THE STRICT SENSE?

Publisher Summary This chapter describes the alpha-adrenoceptor mediated inhibition of noradrenaune secretion. The concept that α 2 -adrenoceptors located on noradrenergic nerve terminals mediate negative feedback control of the noradrenaline concentration in the neuro-effector gaps has become widely accepted. It is found that if α-adrenoceptors control the secretion of NA, then the NA secreted as a result of a priming nerve impulse should induce a transient depression of the secretory responsiveness of the nerve terminals to a subsequent impulse. This depression should decay with time and, therefore, be most prominent on stimulation at high frequency. It is pointed out that the secretion of NA per nerve impulse is usually either independent of or increases with the frequency of nerve stimulation, in most tissues and species. G-blocking agents should not enhance the secretion of NA evoked by a single nerve impulse. NA released by a single pulse cannot retroactively modulate its own release. It is found that while the concept of g-adrenoceptor mediated negative feedback control of NA secretion requires that the blockade of neuronal g-adrenoceptors should enhance the secretion of NA evoked by trains of two or more nerve impulses, it implies that α-blockade should not enhance the secretion of NA caused by a single impulse.