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Role Of Neural Substance P And Coexisting Calcitonin Gene-Related Peptide (Cgrp) In Cardiovascular Function
Published in Geoffrey Burnstock, Susan G. Griffith, Nonadrenergic Innervation of Blood Vessels, 2019
Substance P belongs to a group of polypeptides known as tachykinins. Among these, physalaemin and kassinin have been isolated from amphibian skin, and eledoisin from the salivary glands of a mediterranian octopode. As seen from Table 1, they show considerable homology of their C-terminal amino acids, and they have characteristic biological activities.18 It was generally believed that substance P was the only tachykinin present in mammals, until Lazarus et al.19 found that mammalian tissues also contain physalaemin-like immu-noreactivity. Recently, two novel tachykinins have been isolated from porcine material, namely neurokinin A (also known as substance K) and neurokinin B (also called neuromedin K), having the same C-terminal pentapeptide sequence (Table 1) as the amphibian tachykinin, kassinin.20 Genetic codes have been found for two precursors of substance P, one of which also contains the code for neurokinin A.21 Porcine brain has been shown to store, in addition, a 36-amino acid peptide, which is an N-terminally extended form of neurokinin A and which has been named neuropeptide K (Figure 2).22 This is, with the exception of one amino acid residue, homologous to a portion of the bovine precursor for substance P and neurokinin A reported by Nawa et al.21
Non Adrenergic, Noncholinergic Innervation of Gastrointestinal Vessels
Published in Geoffrey Burnstock, Susan G. Griffith, Nonadrenergic Innervation of Blood Vessels, 2019
Annica B. Dahlström, Ola Nilsson, Ove Lundgren, Håkan Ahlman
In pharmacological doses, SP has been reported to have vasoconstrictive actions as demonstrated in vitro in the inferior mesenteric or portal veins of the rat.57 Comparative studies in vitro on the vasodilator response of gastrointestinal peptides on mesenteric vessels generally showed more pronounced effects of arteries than of veins, with the exception of SP, which caused equipotent responses in both types of vessels.58 SP is also a potent liberator of histamine from mucosal mast cells.59 The vasodilator effects of SP in some vascular beds were reduced after pretreatment with antihistamines, which may indicate a partly indirect mode of action of SP.60 SP receptors have been suggested to be located on the endothelium, which seems to be a prerequisite for mediation of the dilatory responses.61 In vitro studies on the direct action of SP on smooth muscle indicate that SP has in fact indirect effects in most test systems, except in the rabbit mesenteric vein. The SP response in this tissue was unchanged after removal of the endothelium, or after blockade of cholinergic and histami-nergic receptors in combination with inhibition of prostaglandin synthesis.62,63 This vessel had also a characteristic pattern of response with regard to activation of subtypes of tachykinin receptors; the sensitivity to kassinin/eledoisin was higher than to physalaemin/SP.63,64 Studies on the vasodilatory actions of bradykinin have indicated that this peptide may act indirectly by the release of SP, since its actions were partly antagonized by SP analogues.65
Gastroenteropancreatic Regulatory Peptide Structures: An Overview
Published in Edwin E. Daniel, Neuropeptide Function in the Gastrointestinal Tract, 2019
Erspamer233 is generally recognized as being the first to predict that additional mammalian tachykinins remained to be discovered. Subsequently, based on numerous lines of investigation, including differential potencies of the biological effects of different amphibian peptides on administration into mammals, immunologic studies, and ligand-binding studies demonstrating the existence of different types of receptors for tachykinins, a number of researchers presented evidence suggesting the existence of additional mammalian tachykinins (for review see References 238 and 239). These predictions were fulfilled with the isolation of neurokinin-α and neurokinin-β from porcine spinal cord extracts by Kimura and colleagues.240 Both peptides were composed of ten amino acid residues and had C-terminal pentapeptides identical to each other and to the amphibian skin peptide kassinin (see Figure 11A,C). Neurokinin-α and -β have considerable structural differences in the N-terminal halves of their molecules and, hence, are clearly distinct peptides. Independently and almost immediately thereafter, Nawa and colleagues241 reported the deduced sequences of two types of bovine brain substance P precursors from cDNA clones coding for the so-called preprotachykinin A precursor (PPT-A). One PPT-A precursor contained only the sequence of substance P, but the second contained the sequence of a tachykinin-like structure which they termed substance K (named presumably for its structural similarity to kassinin) and which was identical to neurokinin-α.240 Subsequently, Minamino and colleagues242 isolated from porcine spinal cord extracts a peptide identical to neurokinin-α which they designated neuromedin L. Hence, an identical peptide had been identified independently, in rapid succession, by three groups and given three separate names: neurokinin-α, substance K, and neuromedin L. In accordance with current recommendations for the nomenclature of tachykinins,243 in this review this decapeptide is designated neurokinin A or NKA, which is understood to be synonymous with neurokinin-α, substance K, and neuromedin L. A similar problem arose when Kangawa and colleagues244 isolated from porcine spinal cord tissue extracts a peptide identical to neurokinin-β which they termed neuromedin K. Hence, this decapeptide was discovered independently by two groups about the same time, but was given different names. In accordance with the suggestions for tachykinin nomenclature,243 in this review this decapeptide is designated neurokinin B or NKB, but is understood to be synonymous with neurokinin-β and neuromedin K.
Neurokinin receptor antagonism: a patent review (2014-present)
Published in Expert Opinion on Therapeutic Patents, 2020
Substance P (SP), hemokinin-1, neurokinin A (NKA), neurokinin B (NKB), neuropeptide K, eledoisin, ranakinin, and kassinin belong to the tachykinin family of peptides which, via the metabotropic neurokinin (NK)-1, NK-2 and NK-3 receptors, exert many physiological actions and are involved in many pathophysiological mechanisms (e.g. cancer, emesis, anxiety, depression, pain, alcohol addiction, inflammation, viral and bacterial infection, pruritus) [1–3].