Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P20366 (substance P)
 21,176 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Studies were made of the distribution of gut hormones and neuropeptides in the gastrointestinal tract of mice with hereditary aganglionic colon (s1/s1) and their normal littermates. Antisera to substance P, vasoactive intestinal polypeptide, and enkephalins demonstrated markedly diminished numbers of immunofluorescent nerve fibers in the aganglionic segment of colon; in contrast, in proximal colon and small intestine the distribution of peptidergic nerve fibers was essentially normal. Mucosal endocrine cells were demonstrated in the colon by antisera to substance P, somatostatin, glucagon, and cholecystokinin; in each case there were similar numbers of cells in s1/s1 and normal mice. Radioimmunoassays for vasoactive intestinal polypeptide and bombesin showed diminished concentrations of immunoreactive material in the aganglionic segment of colon of 16-17-day-old animals. However, assays for CCK--which is predominantly located in endocrine cells--showed similar concentrations of immunoreactive material throughout the gut of s1/s1 and normal mice. It was of interest that the concentrations of immunoreactive substance P were lower than normal not only in the aganglionic segment of colon, but also in proximal colon and distal small intestine, and that at all ages the development of substance P in the intestine was delayed in the s1/s1 mice. The results are consistent with the idea that the constriction of the aganglionic segment of colon develops as a consequence of lack of intrinsic inhibitory neurons, possibly those containing vasoactive intestinal polypeptide. The presence of an aganglionic segment is attributable to delayed migration of the neuroblasts from the neural crest. Thus the findings of normal populations of gut endocrine cells in the aganglionic segment is further support for the view that the embryologic origin of gut endocrine cells is different to that of gut neurons.
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PMID:Distribution and development of peptidergic nerves and gut endocrine cells in mice with congenital aganglionic colon, and their normal littermates. 617 11

The presence of peptides in the gastrointestinal tract of the rainbow trout, Salmo gairdneri, was investigated immunocytochemically. VIP-like immunoreactivity was demonstrated in nerves in all layers of the stomach and the intestine, whereas substance P-like immunoreactivity was localized to endocrine cells, predominantly in the mucosa of the stomach, and to nerves mainly concentrated in the myenteric plexus throughout the gut. Endocrine cells reactive to gastrin/CCK antiserum were demonstrated in the intestinal mucosa, while no immunoreactivity was found in the stomach. Bombesin-immunoreactive and somatostatin-immunoreactive cells were localized in the stomach mucosa, and cells reactive to glucagon antiserum in the intestinal mucosa. Radioimmunoassay of stomach mucosa and muscle confirmed the presence of VIP-like and substance P-like immunoreactivity in these tissues, while gastrin/CCK-like immunoreactivity was low and bombesin-like immunoreactivity was insignificant. In conclusion, molecules resembling the mammalian brain-gut peptides may be involved in the neuronal and hormonal control of gut function in fish.
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PMID:VIP-, substance P-, gastrin/CCK-, bombesin-, somatostatin- and glucagon-like immunoreactivities in the gut of the rainbow trout, Salmo gairdneri. 617 24

Substance P, somatostatin, VIP, CCK, angiotensin II, and bombesin have all been localized by immunohistochemical or radioimmunological means in neurons of sensory ganglia or in the dorsal horn of the spinal cord. Most of these neuropeptides have electrophysiological effects on spinal neurons and for substance P and somatostatin, these effects have been associated with particular sensory modalities. Newer investigations using the compound capsaicin are consistent with the hypothesis that substance P is an important neurochemical mediator of certain kinds of noxious peripheral stimuli. The newly described substance P antagonists promise to be important pharmacological tools for investigation of the long-neglected neurochemical bases of sensory neuron function. Elaboration of the roles of these sensory neuropeptides will no doubt shed light on many disease states in which there seems to be sensory neuron involvement.
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PMID:Neuropeptides in sensory neurons. 618 Feb 72

The distribution and origin of four peptide neurotransmitter candidates of primary afferents (substance P, SP; somatostatin, SS; cholecystokinin, CCK; and vasoactive intestinal polypeptide, VIP) were studied in the stingray with peroxidase-antiperoxidase (PAP) immunohistochemistry. This elasmobranch has virtually no unmyelinated primary afferents, having instead only large and small myelinated afferents. SP-like immunoreactivity was distributed densely in the superficial aspect of the substantia gelatinosa (SG), particularly laterally, and was scattered in the nucleus proprius, the intermediate zone, and the ventral horn. The distributions of SS-, CCK-, and VIP-like immunoreactivities were similar to each other, but different from that of SP. Stained fibers appeared to issue from a prominent tract in the dorsolateral funiculus to form a plexus at the lateral margin of the nucleus proprius. The fibers spread dorsally and medially through the SG to terminate in a thin band at the superficial margin of the SG. Both SS and CCK were more dense in the lateral third of the SG, while VIP was more diffusely distributed within this structure. The remaining regions of the spinal gray matter contained immunoreactive fibers and terminals in variable densities. Many SS-positive cell bodies were observed in the ventral horn, in the deep dorsal horn, and in the ependymal layer. CCK-positive cells were observed in the medial ventral horn, and VIP-positive cells were observed subjacent to the SG and within the dorsolateral funiculus. After unilateral dorsal rhizotomies, SP-like immunoreactivity in the SG was depleted, while SP staining elsewhere and all SS, CCK, and VIP staining was indistinguishable from control. Thus all four peptides are present in the stingray spinal cord, although only SP appears to be a candidate primary afferent transmitter.
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PMID:Immunohistochemical studies on the distribution and origin of candidate peptidergic primary afferent neurotransmitters in the spinal cord of an elasmobranch fish, the Atlantic stingray (Dasyatis sabina). 618 83

Using specific antisera and immunocytochemical methods VIP, CCK, substance P, methionine-enkephalin, neurotensin and somatostatin-like immunoreactive fibers were found within the fornix and fimbria in 3 species (rat, monkey and human). Neither methionine-enkephalin- nor substance P-containing cell bodies were located within the hippocampus and so fibers containing these peptides are presumably hippocampal afferents, probably arising in the septum or caudal hypothalamus. VIP, CCK, neurotensin and somatostatin fibers may be hippocampal efferents arising from cell bodies within the subiculum.
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PMID:Immunocytochemical localization on neuropeptides in the fornix of rat, monkey and man. 618 16

Gastrins and cholecystokinins contract the isolated taenia coli of the guinea-pig. Porcine CCK-39 produced the greatest contractile response and human gastrin-17 I and -34 the weakest. Pentagastrin had the highest affinity to the receptors and non-sulphated CCK-8 the lowest. The contractions produced by the CCK peptides were reduced by the neuronal blocker tetrodotoxin and by the muscarinic blocker atropine but not by the substance P antagonist [D-Pro2,D-Trp7,9]SP. It is concluded that gastrin/CCK peptides act directly on smooth muscle cells and that in addition these peptides, notably sulphated forms of CCK, are capable of exciting cholinergic neurons (but not SP neurons) to cause smooth muscle contraction.
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PMID:Gastrins and cholecystokinins release acetylcholine but not substance P from neurons in the guinea-pig taenia coli. 619

Substance P (SP) (10(-8) M) can rapidly reduce the affinity and increase the density of 3H-5-HT binding sites in spinal cord membranes. CCK-8 and CCK-4 (10(-8) M) can rapidly and differentially change the characteristics of 3H-spiperone striatal binding sites linked to DA receptors of the D2 type. CCK-4 increase and CCK-8 reduce the number of striatal binding sites for 3H-spiperone, indicating for the first time separate CCK-4 binding sites. CCK-4 (10(-8) M) but not CCK-8 (10(-8) M) can rapidly reduce the affinity and increase the number of the 3H-spiperone binding sites linked to 5-HT receptors of the dorsal cerebral cortex of rats. CCK-8 (10(-8) M) only produces a trend for a small increase in the Bmax values of these receptors. These results again imply the existence of separate CCK-4 binding sites in this case in the cerebral cortex. Glutamate (10(-6) M), but not N-methyl-D-aspartate (10(-6) M) can rapidly change the characteristics of the 3H-N-propylnorapomorphine (3H-NPA) binding sites in striatal membranes of rats. Glutamate (10(-6) M) increases the density and especially reduces the affinity of the 3H-NPA binding sites, which label D2 and D3 types of DA receptors. Taken together the present findings give evidence that neuropeptide receptors and glutamate receptors can in vitro rapidly modulate the characteristics of different types of DA and 5-HT receptors by way of receptor--receptor interactions at the comodulate level or at the local circuit level. It is hypothesized that these receptor--receptor interactions are of importance for the encoding of short-term memory.
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PMID:Evidence for the existence of receptor--receptor interactions in the central nervous system. Studies on the regulation of monoamine receptors by neuropeptides. 619 8

Neuropeptides were first localized in the human spinal cord by immunocytochemistry and substance P has been shown, by the same method, to be reduced ipsilaterally in the dorsal horn after limb amputation and bilaterally in the Riley-Day syndrome. Several neuropeptides increasingly fulfil the criteria to establish them as neurotransmitters or neuromodulators, and they may also have trophic actions in the spinal cord. Using radioimmunoassay and immunocytochemistry, we present here for the first time a quantitative regional distribution and localization of vasoactive intestinal polypeptide (VIP), substance P, somatostatin, bombesin and cholecystokinin (CCK-8) in normal postmortem human spinal cord. A comparison of the distribution of these peptides reveals an exceptional pattern for VIP, with relatively much higher levels in the lumbosacral region. Immunocytochemical analysis shows a distinctive distribution of VIP-containing fibres and terminals at the lumbosacral segments. This VIP-containing system may have an important role in the spinal control of urogenital function in man.
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PMID:A VIP-containing system concentrated in the lumbosacral region of human spinal cord. 619 28

The contractile response of the isolated guinea-pig ileum to cholecystokinin octapeptide (CCK-8) that remained in the presence of atropine was greatly inhibited by the substance P antagonist D-Pro2,D-Trp7,9-substance P. This indicates that the atropine-resistant contraction to CCK-8 is mediated by the release of substance P from enteric neurones. Activation of alpha-adrenergic receptors by noradrenaline, clonidine or mesenteric sympathetic nerve stimulation inhibited the atropine-resistant contraction to CCK-8 but did not affect the contractile effect of substance P. It is concluded that alpha-adrenergic receptors exert an inhibitory influence on the release of substance P from enteric neurones.
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PMID:Sympathetic control of substance P releasing enteric neurones in the guinea pig ileum. 619 59

Immunohistochemical studies of the vas deferens and seminal vesicle of mouse, guinea-pig, and rabbit showed the presence of nerve fibres containing vasoactive intestinal polypeptide (VIP), substance P (SP), and gastrin-releasing peptide (GRP) supplying the smooth muscle layers as well as blood vessels. The nerve supply was better developed in the seminal vesicle than in the vas deferens. The motor activity of the vas deferens and seminal vesicle of the guinea-pig was studied in vitro. The vas deferens responded to transmural electrical stimulation with a twitch followed by a slow contraction. The twitch was blocked by guanethidine and tetrodotoxin, but not by atropine, propranolol, phenoxybenzamine, or fluphenazine. The slow contraction exhibited features of an alpha-receptor-mediated response. SP, physalaemin and eledoisin contracted the smooth muscle and also potentiated the twitch response to electrical nerve stimulation in a concentration-dependent manner. The SP blocking agent, (D-Pro2,D-Trp7,9)-SP, affected neither the resting tension nor the response to electrical stimulation. It is therefore suggested that the SP fibres act mainly prejunctionally. VIP, Leu-enkephalin, cholecystokinin octapeptide (CCK-8), angiotensin II, vasopressin, neurotensin, bombesin, and GRP had no effect on either the resting tension or the response to electrical nerve stimulation. The seminal vesicle responded to electrical stimulation with a contraction which was unimpaired by atropine, propranolol, phenoxybenzamine, and guanethidine, but abolished by tetrodotoxin. Hence, this contraction is mediated by a non-adrenergic, non-cholinergic neurotransmitter. Bombesin, GRP, SP, physalaemin and eledoisin contracted the smooth muscle and potentiated the response to electrical stimulation. VIP, Leu-enkephalin, CCK-8, angiotensin II, vasopressin, and neurotensin had no effect on the resting tension or on the response to transmural electrical stimulation. The SP antagonist abolished the contraction elicited by SP but did not influence the response to nerve stimulation. The results suggest that the SP and GRP nerves may have prejunctional and facilitating postjunctional effects in the seminal vesicle.
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PMID:Immunohistochemical localization of substance P, vasoactive intestinal polypeptide and gastrin-releasing peptide in vas deferens and seminal vesicle, and the effect of these and eight other neuropeptides on resting tension and neurally evoked contractile activity. 619 10


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