Drug‐induced changes in the release of [³H]‐noradrenaline from field stimulated rat iris

The EFFECT OF STIMULUS INTENSITY ON Α‐ADRENOCEPTOR‐MEDIATED FEED‐BACK CONTROL OF NORADRENALINE RELEASE

“…have been recorded during exposure to phentolamine at concentrations of 1 x 10' M and 1.8 x 10' M by Farnebo & Hamburger (1971) and by de Potter, Chubb, Put & de Schaepdryver (1971) respectively and we have now investigated this quantitative discrepancy between our results and those of these other workers.…”

Sixth Gaddum Memorial Lecture National Institute for Medical Research, Mill Hill, January 1977

“…The reduction i,a transmitter release obtained by exposure to a-receptor agonists was equally observed in tissues in which the response of the effector organ is mediated by a-receptors (Kirpekar, Furchgott, Wakade & Prat, 1973;Starke et al, 1974;Starke et al, 1975a;Langer et al, 1975a) or by ,-receptors (Starke, 1972b;Langer et al, 1972b;Rand, McCulloch & Story, 1975 (Langer, 1970;De Potter et al, 1971;Farnebo & Hamberger, 1971a;Starke et al, 1971;Enero et al, 1972; Dubocovich Farah & Langer, 1974;Cubeddu et al, 1974;Langer, 1974b; (Enero & Langer, 1973;Cubeddu & Weiner, 1975). Consequently it appears that when the concentration of released noradrenaline in the synaptic cleft falls below a certain threshold, it fails to trigger the presynaptic negative feed-back mechanism that regulates noradrenaline release.…”

“…According to this hypothesis presynaptic a-adrenoceptors are involved in the regulation of noradrenaline release through a negative feed-back mechanism mediated by the neurotransmitter itself. As shown schematically in Figure 2, noradrenaline released by nerve stimulation, once it reaches a threshold concentration in the synaptic gap, activates presynaptic a-adrenoceptors, triggering a negative feed-back mechanism that inhibits further release of the transmitter Farnebo & Hamberger, 1971a;Enero et al, 1972;Starke, 1972a, b;Rand, Story, Allen, Glover & McCulloch, 1973;Langer, 1973;Langer, 1974b).…”

Dopamine‐induced Depression of Adrenergic Nerve‐mediated Contraction of Smooth Muscle

“…It is well documented that a-adrenoceptor agonists depress and a-adrenoceptor antagonists increase the release of noradrenaline from adrenergic axons in response to nerve stimulation (Farnebo & Hamberger, 1971;Kirpekar & Puig, 1971;Starke, 1972 and others), suggesting the existence of presynaptic aadrenoceptors. From such data it has been postulated that these receptors may be involved in feedback modulation of adrenergic transmission (Farnebo & Hamberger, 1971;Starke, 1971;Kirpekar & Puig, 1971).…”

“…From such data it has been postulated that these receptors may be involved in feedback modulation of adrenergic transmission (Farnebo & Hamberger, 1971;Starke, 1971;Kirpekar & Puig, 1971). Recently it has been reported that low concentrations of dopamine also depress transmitter overflow from the rabbit ear artery (McCulloch, Rand & Story, 1973).…”