Long‐term regulation of synaptic acetylcholine release and nicotinic transmission: the role of cyclic AMP

Abstract

1 Using the rat superior cervical ganglion in vitro, the relative efficacy of nicotinic synaptic transmission was estimated by recording the postganglionic compound action potential and the amount of endogenous acetylcholine (ACh) released. These two parameters were correlated in individual ganglia by sampling the bathing medium for the assay of ACh while simultaneously recording the postganglionic response.2 The P-adrenoceptor agonist isoprenaline potentiated both the evoked release of ACh and the postganglionic response by about 20% during preganglionic stimulation at 0.2 Hz. 3 The adenosine receptor agonist 2-chloroadenosine inhibited ACh release and the postganglionic response by about 35%. 4 Tetanic preganglionic stimulation for a few seconds induced a long-term potentiation of nicotinic responses and of ACh release. Both of these potentiations were dependent upon extracellular Ca2l during the tetani. 5 Forskolin and analogues of cyclic AMP also caused a long-lasting potentiation of both the evoked release ofACh and the postganglionic response, indicating that cyclic AMP may regulate transmission by a presynaptic mechanism. The specificity of the cyclic AMP analogues was tested using various butyryl-and bromo-purine nucleotides. 6 The effects of forskolin and 8-bromo-cyclic AMP did not appear to be dependent upon extracellular Ca2+. 7 The potentiation caused by forskolin was consistently augmented by three phosphodiesterase inhibitors -AH 21-132, papaverine and SQ 20-006. However, the effect of forskolin was not consistently enhanced by theophylline, nor was it reduced by the adenylate cyclase inhibitor SQ 22-536. 8 The neurogenic long-term potentiation was augmented by two of the phosphodiesterase inhibitors that also augmented the forskolin-induced potentiation -papaverine and SQ 20-006. 9 It was concluded that cyclic AMP can enhance nicotinic transmission, and can do so by increasing the evoked release of ACh. However, it was not possible to prove that cyclic AMP mediates the longterm potentiation induced by tetanic preganglionic stimulation.

Long-term increases in neurotransmitter release from neuronal cells expressing a constitutively active adenylate cyclase from a herpes simplex virus type 1 vector.

“…The increase in release was probably from neurons; glia do not synthesize, accumulate, or secrete significant amounts of catecholamines (28). Forskolin caused a short-term increase in release, consistent with reports (8,29).…”

“…In sympathetic neurons, activation of the cAMP pathway causes multiple short-term changes in neuronal function, including increased NT release (1,2,8). Several long-term changes in sympathetic neuron physiology, including one termed long-term facilitation (32), have been described (29,32). Relatively stable changes in the cAMP pathway mediate long-term changes in the physiology of specific central nervous system neurons, such as the norepinephrine cells in the locus coeruleus (34).…”

PKG and PKA Signaling in LTP at GABAergic Synapses

“…A rise in presynaptic cAMP following activation of adenylyl cyclase facilitates neurotransmitter release at many synapses, and is involved in the induction and expression of LTP at many excitatory and inhibitory synapses (Briggs et al , 1988; Greengard et al , 1991; Cameron & Williams, 1993; Chavez-Noriega & Stevens, 1994; Huang & Kandel, 1994; Weisskopf et al , 1994; Bonci & Williams, 1996; Salin et al , 1996a; Bonci & Williams, 1997; Huang & Kandel, 1998; Castro-Alamancos & Calcagnotto, 1999; Linden & Ahn, 1999; Mellor et al , 2002). Furthermore, PKA activation has previously been demonstrated to potentiate GABA A R synapses on VTA dopamine neurons (Melis et al , 2002).…”

Role of Long-Term Potentiation of Sympathetic Ganglia (gLTP) in Hypertension

“…Nearly 10 years after the term long-term potentiation (LTP) was coined by Bliss and Lomo (3) in the hippocampal formation, LTP was described in the superior cervical sympathetic ganglia (SCG) (4,5). Ganglionic LTP (gLTP) was later demonstrated in various sympathetic ganglia in different animal species in vitro and in situ (4)(5)(6)(7)(8)(9)(10)(11)(12)(13). Another decade passed before the existence of a very similar gLTP in the avian parasympathetic ciliary ganglion was reported (14).…”