Non-adrenergic Non-cholinergic Autonomic Transmission
Kenneth J. Broadley in Autonomic Pharmacology, 2017
Somatostatin (SS) is mainly released from endocrine cells where it has a paracrine function to inhibit adjacent endo- or exocrine cells (see Figure 8.3 for gastrin release). Additionally, SS immunoreactivity has been identified in the gut, its release from which is induced by distension. Since this is only partly inhibited by TTX, it is uncertain how much of this is from endocrine cells rather than from neurones. Finally, calcitonin gene-related peptide (CGRP) and galanin are two peptides located in the intrinsic neurones of the gastrointestinal tract. CGRP is also located in primary afferent neurones, is a potent vasodilator, and contributes to the neurogenic vasodilatation in inflammatory responses (see later). CGRP and galanin are probably not involved in efferent autonomic functions.
The Role of Neuropeptides in the Normal and Pathophysiological Control of Blood Flow
Edwin E. Daniel in Neuropeptide Function in the Gastrointestinal Tract, 2019
In some tissues, CGRP may be capable of modulating sympathetic nerve function. Studies involving the vas deferens indicate that low subvasoactive concentrations of CGRP are capable of inhibiting nerve-mediated noradrenergic contractile responses.29 Although it was suggested that presynaptic CGRP receptors inhibiting the release of NA could be responsible for these effects,29 subsequent studies have indicated that concentrations of CGRP inhibiting nerve-mediated contractile responses in the vas deferens did not alter the release of [3H]NA from the noradrenergic nerves.30 Electrophysiological studies indicate that the inhibitory effects of CGRP are mediated postsynaptically. In these studies it was demonstrated that CGRP did not affect the amplitude of excitatory junction potentials (EJPS), but increased the threshold membrane potential (to more positive values) required to initiate an action potential and slightly reduced the contractile responses produced by topically applied NA and adenosine triphosphate (ATP).31 It was concluded that CGRP produced its inhibitory effects by suppressing smooth muscle cell (SMC) excitability and excitation-contraction coupling. At present, the electrophysiological effects of CGRP on vacular smooth muscle (VSM) have not been studied. However, it is possible that the mechanisms of CGRP action on blood vessels are similar to those observed in the vas deferens.
Atrial Natriuretic Peptide (Anp), Neuropeptide Y (Npy), And Calcitonin Gene-Related Peptide (Cgrp) In The Cardiovascular System Of Man And Animals *
Geoffrey Burnstock, Susan G. Griffith in Nonadrenergic Innervation of Blood Vessels, 2019
Calcitonin gene-related peptide or CGRP was found incidentally by Rosenfeld and colleagues during their analysis of the calcitonin gene.62 They observed that as well as the complete sequence of calcitonin and its flanking peptides, there resided the coding sequence of another quite distinct peptide which was thus termed calcitonin gene-related peptide. After transcription of the heterogeneous messenger RNA, the specific messenger for CGRP is expressed mainly in neural tissue. CGRP is broadly distributed in the central and peripheral nervous systems.64 In the latter, particularly high concentrations are found in the sensory nervous system.63, 64 CGRP is found in large concentrations in the dorsal root ganglion, in primary sensory neurons with central branches terminating in the dorsal horn of the spinal cord, and some of their peripheral branches terminating in the cardiovascular system.65-67 Substance P and CGRP occur together in a subpopulation of CGRP-containing primary sensory neurones.63, 68
Drug profile: galcanezumab for prevention of cluster headache
Published in Expert Review of Neurotherapeutics, 2021
Dharani Mudugal, Teshamae S. Monteith
CH has a complex pathophysiological mechanism. Activation of the trigeminovascular system is pivotal in causing the pain in part by the release of neuroinflammatory peptides such as CGRP, substance P, vasoactive intestinal peptide [VIP], and pituitary adenylate cyclase-activating peptide [PACAP] [32]. CGRP belongs to the calcitonin family of peptides and is produced in central and peripheral neurons. It exists as two isoforms in humans. The alpha subunit is a long 37 amino acid peptide formed by alternate splicing of the CALCA [calcitonin related polypeptide alpha gene] on chromosome 11. Little is known regarding the beta isoform [33]. Based on this assumption that CGRP may be a key effector molecule in the pathophysiology of CH, several randomized placebo-controlled trials have examined the role of CGRP monoclonal antibodies in the treatment of CH.
Menstrual migraine: a review of current and developing pharmacotherapies for women
Published in Expert Opinion on Pharmacotherapy, 2018
G. Allais, Giulia Chiarle, Silvia Sinigaglia, Chiara Benedetto
CGRP, a neuropeptide composed of 37 amino acids, is ubiquitous in the human body but prevalently localized on C sensory fibers [28]. CGRP is a major vasodilator, mediator of neurogenic inflammation, and modulator of nociceptive stimuli: when released in the periphery of activated trigeminal nociceptive terminals, it causes edema, increases blood flow, and activates inflammatory cells. In the synapses of the trigeminocervical complex, it centrally transmits nociceptive stimuli via the brainstem to the thalamus and the somatosensory cortex, generating hyperalgesia [27,29]. Several studies have demonstrated that during a migraine attack CGRP levels are elevated in the external jugular vein ipsilateral to the side affected by the headache [116,117] and in saliva during both spontaneous and nitric oxide-induced attacks [118]. In addition, elevated levels of CGRP were found in patients with chronic migraine also during intercritical intervals [119]. Intravenous administration of the isoform of human αCGRP was observed to induce migraine or similar disorders in patients diagnosed with migraine [120].
Communication between the gut microbiota and peripheral nervous system in health and chronic disease
Published in Gut Microbes, 2022
Tyler M. Cook, Virginie Mansuy-Aubert
Along with immune cells, enteric, spinal, and vagal neurons express toll-like receptors (TLRs). Disrupted TLR signaling in peripheral neurons may contribute to deficits in enteric nervous development, gut motility, immunity, and visceral perception (Figure 4). LPS binds to toll-like receptor 4 (TLR4) and LTA binds TLR2. TLR2 expressed in spinal sensory neurons and activation can alter the reflex release of neuropeptides capable of increasing cytokines.67 TLR4 is expressed in vagal neurons which play a key role in the inflammatory reflex where the brain senses potential proinflammatory signals and regulates the immune responses.67,68 This is accomplished by vagal efferent release of acetylcholine onto immune cells in target tissues which can dampen the local immune response. Additionally, vagal TLR4 signaling mediates LPS-induced release of the neuropeptide calcitonin gene-regulated peptide (CGRP).69 CGRP is a vasodilatory neuropeptide released by spinal and vagal afferent neurons, as well as enteric neurons, which contributes to inflammation resolution and pain.70
Related Knowledge Centers
- Adrenomedullin
- Alternative Splicing
- Amylin
- Calcitonin
- Chromosome 11
- Peptide
- Amino Acid
- Vasodilation
- Melanocyte-Stimulating Hormone
- Neuron