The EFFECT OF DIFFERENT CALCIUM CONCENTRATIONS ON THE INHIBITORY EFFECT OF PRESYNAPTIC Α‐ADRENOCEPTORS IN THE RAT VAS DEFERENS

Canada1 The relation of calcium ion influx into nerve terminals to presynaptic adrenoceptor function and the possible masking, by desensitization due to intraneuronal calcium accumulation, of the effects of adrenoceptor agonists and antagonists on presynaptic a-adrenoceptors was investigated in guineapig atria previously incubated with [3H]-noradrenaline. 2 Atria were stimulated with 100 pulses at various frequencies (ito 15Hz) in standard (2.3mM), low (0.26 mM) and high (6.9 mM) calcium-Krebs solution in the absence and then the presence first of noradrenaline and subsequently phenoxybenzamine. 3 The per pulse overflow of tritium was directly related to the calcium concentration of the Krebs solution, being much reduced and substantially increased in 0.26 and 6.9 mm calcium-Krebs solutions respectively. 4 Noradrenaline inhibited the overflow of tritium in low calcium-Krebs solution, to a relatively constant extent, independently of frequency. In addition, the agonist had a greater maximal inhibitory effect in standard than in reduced calcium-Krebs. The catecholamine was as effective an inhibitor of overflow at the lowest and highest frequencies in high as it was in standard calcium-Krebs solution. Phenoxybenzamine invariably increased the tritium overflow but was generally less effective both in low and in high calcium-Krebs solution. The patterns of inhibition and enhancement of stimulation-induced tritium overflow by these two agents do not indicate an intimate relationship between calcium influx and adrenoceptor activation; nor does desensitization appear to be an adequate explanation of the relationship between frequency of stimulation and the intensity of agonist and antagonist effect in the three different calcium concentrations. 5 It is concluded that the perineuronal levels of adrenergic transmitter do not establish the magnitudes of effect of exogenous adrenoceptor agonists and antagonists on tritium overflow and that a negative feedback regulation of release by transmitter is exceedingly unlikely under ordinary conditions of neurotransmission.

Section: Discussionmentioning

confidence: 99%

The Role of Calcium in the Effects of Noradrenaline and Phenoxybenzamine on Adrenergic Transmitter Release From Atria: No Support for Negative Feedback of Release

Kalsner

1981

“…However, this depression may be due to a growing nicotinic receptor-mediated autoinhibition of acetylcholine release during a train (Miledi, Molenaar & Polak, 1978). A growing autoinhibition of NA release during a train has also been suggested, in which the NA released by an impulse acts on the nerve terminal to decrease the entry of Ca ions during a subsequent impulse, thus counteracting the effects of residual CaX (Stjarne, 1973;Bennett & Middleton, 1975b;Starke, 1977;Drew, 1978).…”

Section: Discussionmentioning

confidence: 99%

An Electrophysiological Analysis of the Effects of Morphine on the Calcium Dependence of Neuromuscular Transmission in the Mouse Vas Deferens

Bennett

Lavidis

1980

1 The effects of morphine on the Ca-dependence of the synaptic potential amplitude in the mouse vas deferens have been determined.2 The synaptic potential increased with a power factor of 2.4 for [Ca]. between 0.7 mm and 1.8 mm.Morphine (40 nM) decreased the synaptic potential, without altering the second power relationship between the synaptic potential and [Ca]0. 3 Morphine reversed the depression in the synaptic potential which develops during a short highfrequency (10 Hz) train of impulses to facilitation. Consequently the synaptic potential beyond the tenth impulse was unaffected by morphine. 4 Morphine did not alter the facilitation of the synaptic potential which develops during a short low-frequency (<2 Hz) train of impulses in normal [Ca]0. Consequently morphine decreased the synaptic potential for each impulse by about the same percentage amount. 5 Morphine increased the small facilitation in the synaptic potential which occurs during a short low-frequency (< 2 Hz) train of impulses in high [Ca]0. This facilitation approximated the predictions based on the assumption that each impulse leaves residual Ca ions bound to receptors involved in transmitter release from the nerve terminal.

“…Thus, the degree of inhibition is dependent upon pulse frequency and upon the Ca2+ concentration of the medium (Drew, 1978) and clonidine inhibits noradrenaline release from the mouse vas deferens following low frequency stimulation (Marshall, Nasmyth & Shepperson, 1977). Furthermore, both epididymal and prostatic portions of the vas deferens are inhibited by clonidine (Brown, McGrath & Summers, 1979).…”

Section: Discussionmentioning

confidence: 99%

Effects of Metoclopramide and Isoprenaline in the Rat Vas Deferens; Interactions With Α‐adrenoceptors

Spedding

1980

3 From these results it is concluded that metoclopramide (2.8 to 280 pM) is a presynaptic a-adrenoceptor antagonist in the rat vas deferens.4 Following,-adrenoceptor blockade with (±)-propranolol (3.3 gM), (--isoprenaline (0.47 to 14 gM) inhibited responses to field stimulation but not to phenylephrine. These propranolol-resistant effects of isoprenaline were antagonized by metoclopramide (2.8 to 280 pM) and by phentolamine (0