Chapter 3 - Cotransmission in the autonomic nervous system
Section snippets
Early studies
For many years, understanding of neurotransmission incorporated the concept that one neuron releases only a single transmitter, termed “Dale’s Principle” by Eccles (1957). This idea arose from a widely adopted misinterpretation of Dale’s suggestion in 1935 that the same neurotransmitter was stored in and released from all terminals of a single sensory neuron, a suggestion which did not specifically preclude the possibility that more than one transmitter may be associated with the same neuron (
Sympathetic nerves
There is compelling evidence that under certain conditions in vitro, single sympathetic neurons may release NA, ACh, or a mixture of these two transmitter substances (Le Douarin et al., 1975, Furshpan et al., 1976, Patterson et al., 1976). It seems likely that this represents a true reflection of events that occur in vivo during perinatal development (Hill and Hendry, 1977). It appears that a population of sympathetic nerve cells are present at birth that have the potential to synthesize both
Parasympathetic nerves
Evidence was presented for seasonal changes in release of ACh, 5-HT, histamine, and a peptide from vagus nerves supplying the frog stomach (Singh, 1964). The evidence for cotransmission of ACh and vasoactive intestinal polypeptide (VIP) in certain postganglionic parasympathetic neurons comes from pharmacological studies performed by Lundberg (1981) on cat salivary glands (see Fig. 3.2B). ACh and VIP are released from the same parasympathetic nerve terminals in response to transmural nerve
Sensory-motor nerves
The neuropeptides substance P (SP) and calcitonin gene-related peptide (CGRP) are the principal transmitters of primary afferent nerves and have been shown to coexist in the same terminals (Gibbins et al., 1985, Rubino and Burnstock, 1996). Furthermore, with the use of colloidal gold particles of different sizes, they have been shown to coexist in the same large granular vesicles (Gulbenkian et al., 1986). The motor (efferent) function of sensory nerves has been demonstrated in rat mesenteric
Intrinsic enteric and cardiac neurons
Intrinsic neurons exist in most of the major organs of the body. Many of these are part of the parasympathetic nervous system, but certainly in the gut, and perhaps also in the heart and airways, some of these intrinsic neurons are derived from neural crest tissue, which differs from that which forms the sympathetic and parasympathetic systems, and appear to participate in local reflex actions independent of the CNS.
The enteric nervous system contains several hundred million neurons located in
Physiological significance of cotransmission
In general, autonomic cotransmission offers more diverse physiological control by mechanisms other than the all-or-none control by messages coming from the CNS that was the dominant view for many years (see Burnstock, 2004, Burnstock, 2009a) (Fig. 3.3).
Cotransmitter plasticity
Neurons possess the genetic potential to produce many neurotransmitters. The particular combination and quantity that results is partly preprogrammed and partly determined by “trophic” factors that trigger the expression or suppression of the appropriate genetic machinery. A number of studies have demonstrated plasticity of expression of autonomic nerves during development and aging, following trauma or surgery, after chronic exposure to drugs and in disease (Burnstock 1990c, Burnstock, 2006,
Concluding comments
A compelling body of evidence is now available to support the cotransmitter hypothesis, which implies more sophisticated local control mechanisms than were envisaged in earlier times. However, a number of issues still need to be resolved, including:
- 1.
resolution of the different roles of coexisting substances (including neurotransmitter, pre- and postjunctional neuromodulator and/or trophic roles) under different physiological conditions and patterns of discharge in the nerves
- 2.
identification of
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Peripheral autonomic nervous system
2022, Primer on the Autonomic Nervous System, Fourth EditionATP as a cotransmitter in sympathetic and parasympathetic nerves - another Burnstock legacy
2021, Autonomic Neuroscience: Basic and ClinicalCitation Excerpt :Shortly beforehand he had proposed that ATP is an inhibitory neurotransmitter in the enteric nervous system of the gastrointestinal tract (Burnstock, 1972) and in the 1980s his and other groups provided the initial evidence that ATP is also coreleased as an excitatory cotransmitter with NA from postganglionic sympathetic nerves innervating the vas deferens, most arteries and other smooth muscle tissues, and with ACh from postganglionic parasympathetic nerves, particularly in the urinary bladder. Now, cotransmission is recognised to occur in varying degrees in a tissue-dependent manner throughout the autonomic nervous system (Burnstock, 2013). Here I will discuss the evidence that supports these neurotransmitter roles and where appropriate, discuss more recent developments.
Resting cardiac sympathetic firing frequencies suppress terminal norepinephrine transporter uptake
2021, Autonomic Neuroscience: Basic and ClinicalCitation Excerpt :However, we did not explore the exact downstream intracellular pathways activated by α2AR to reduce NET rate, thus it would warrant further investigation to elucidate the pathways for the effect observed. There are a host of regulatory mechansism for sympathetic junctional transmission, including feedback mechanisms mediated by NPY and other co-transmitters [for review, see Burnstock, 2013], but amongst these the α2AR-mediated pathways are central (Stjärne, 1989). The α2-AR is an important suppressor of NE release and their dysfunctions are often associated with sympathetic overactivity (Gilsbach and Hein, 2012), thus one would query the its functional role to reduce NET suppression during AP propagation.
Physiopharmacological properties of the testicular capsule: A concise review
2020, European Journal of PharmacologyCitation Excerpt :Besides noradrenaline, postganglionic adrenergic nerves supplying smooth muscle in different organs also store and release the co-transmitter ATP, which in turn modulates contractile responses via pre- and/or postsynaptic purinergic receptors. The role of ATP as a co-transmitter has been investigated in the testicular capsule in several studies (for review see Burnstock, 2013). It was reported that neuronally-evoked contractions of rat and human testicular capsule were not affected by high concentrations of the P2 receptor antagonists suramin or PPADS, (Banks et al., 2006; Jurkiewicz et al., 2006).
Homeostatic systems, biocybernetics, and autonomic neuroscience
2017, Autonomic Neuroscience: Basic and ClinicalThe autonomic nervous system and cancer
2017, Biocybernetics and Biomedical EngineeringCitation Excerpt :In addition the ANS secretes vasoactive intestinal polypeptide (VIP, and from the sympathetic branch neuropeptide Y) and from sensory nerves calcitonin gene-related peptide (CGRP) and tachykinins [94,95]. These peptides may serve as cotransmitters with acetylcholine and noradrenaline with interactions both at pre- and post-synaptic junctions [94,96,97]. Other autonomic transmitters may include GABA, 5-HT, ATP, and dopamine [98–100].