Factors influencing transmission at adrenergic synapses

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%

“…Hughes, 1972;Chan & Kalsner, 1979a). Kirpekar (1975) suggested that intraneuronal accumulation of calcium may also account for the refractoriness of release during intensive nerve stimulation.…”

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

“…without a concomitant increase of the levels of plasma NA, also indicates that the enzyme has its origin in the adrenal, since it is well known that these drugs act mainly on the adrenergic nerve terminals, and not in the adrenal medulla (Kirpekar, 1975).…”

Section: Discussionmentioning

confidence: 98%

“…The potentiation of the rise of plasma DBH activity seen after guanethidine may be due to a reflex, augmented discharge of the adrenal, in order to compensate the hypotension produced by sympathetic neurotransmission blockade at the vascular neuro-effector junction; in the case of phenoxybenzamine, its well known blocking effects on post-and presynaptic a-adrenoceptors can contribute to the overall effect (Kirpekar, 1975).…”

Section: Discussionmentioning

confidence: 99%

Origin of Guinea‐pig Plasma Dopamine Β‐hydroxylase

Arnaiz¹,

Garcı́a²,

Horga³

et al. 1980

Exposure of guinea-pigs to a C02-enriched atmosphere (20% C02, 25% 02, 55% N2) for I to 5 h caused a marked, progressive increase of plasma dopamine f3-hydroxylase (DBH) activity which reached its peak after 2 h of CO2 exposure and then gradually decreased. The increase was abolished by mecamylamine administration before exposure to CO2. Plasma levels of noradrenaline (NA) also increased after CO2 exposure. 2 Guanethidine administration, before exposure to C02, abolished the increase of plasma NA but potentiated the increase of circulating DBH. Phenoxybenzamine injection, before exposure to CO2, also potentiated the increase of plasma enzyme activity. In both cases, DBH activity was increased to almost 10 times the basal circulating enzyme levels. 3 Injection of 6-hydroxydopamine (6-OHDA) caused a pronounced decrease of DBH activity in the right atrium, thoracic aorta and spleen; the adrenal enzyme activity was unchanged. Exposure to CO2 of 6-OHDA-treated animals still evoked a dramatic increase of plasma DBH activity comparable to that found in control animals. 4 The increase of plasma DBH activity evoked by exposure to CO2 of adrenalectomized animals was considerably diminished. 5 These data suggest that in the guinea-pig, the adrenal is the main source of the increase of circulating DBH activity evoked by exposure of the animals to a CO2-enriched gas mixture.

“…In this study both ej.ps and families of d.es have been used to examine the effects of prejunctional modulation of transmitter release by drugs acting on prejunctional at-adrenoceptors and to see if this modulation interacts with a system of endogenous negative feedback. To this end, the relationship between the m-adrenoceptor agonist clonidine and aadrenoceptor antagonist yohimbine and the amount of endogenous transmitter present has been measured when the amount of endogenous transmitter in the junction has been varied by altering the extracellular calcium concentration (Rubin, 1970;Rahamimoff, 1970;Kirpekar, 1975) and by using very low frequency ) The Macmillan Press Ltd 1986 stimulation (Kalsner, 1979;Kuriyama & Makita, 1983).…”

Section: Introductionmentioning

confidence: 99%

Interactions between the effects of yohimbine, clonidine and [Ca]_o on the electrical response of the mouse vas deferens

Blakeley

Mathie

Petersen

1986

Excitatory junction potentials (e.j.ps) were recorded from mouse vas deferens and resolved into families of ‘discrete events’ (d.es) reflecting intermittent release of packets of transmitter from one or a few sites. Within families d.es vary in amplitude between a few preferred values unaffected by any treatments used in these experiments. As [Ca]o is raised from 1.1 to 4.0 mm there is a rise in d.e. amplitude due to an increase in the frequency of large events and a decrease in that of small. At all [Ca]o clonidine reduces d.e. amplitude by increasing failures and small events and decreasing large events. Yohimbine has opposite effects. Both drug effects are concentration‐dependent in the range 5 × 10−9‐10−6 m. As [Ca]o is raised from 1.1 to 4.0 mm, and therefore more natural agonist is released, clonidine becomes more effective at altering d.e. amplitude whereas yohimbine becomes less so. With very low frequency stimulation yohimbine elevates e.j.p. amplitude only if [Ca]o is below 1.6 mm. These results are not easily compatible with the notion that yohimbine breaks a ‘negative feedback’ control of transmitter release.