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

Electrical field stimulation (EFS)-induced non-adrenergic non-cholinergic (NANC) relaxation responses in the rabbit vaginal wall were investigated. These NANC responses were partially inhibited with the nitric oxide synthase (NOS) inhibitors N(G)-nitro-L-arginine methyl ester (L-NAME; 500 microM), N(G)-nitro-L-arginine (300 microM) or N-iminoethyl-L-ornithine (500 microM) or the selective soluble guanylate cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3,-a]quinoxalin-1-one (ODQ, 10 microM). Application of L-NAME and ODQ concomitantly did not increase the degree of inhibition. L-NAME or ODQ were observed to be more effective at low frequencies. The resistant part of the responses was more pronounced at higher frequencies and was completely inhibited by tetrodotoxin (1 microM). Exogenous application of the peptides vasoactive intestinal peptide (VIP), pituitary adenylate cyclase activating peptide (PACAP-27 and PACAP-38), peptide histidine methionine (PHM), peptide histidine valine (PHV), helospectin-I or -II induced a relaxation response. Calcitonin gene-related peptide or substance P did not cause any relaxation. The peptidase alpha-chymotrypsin (type II; 2 units ml(-1)) did not affect non-nitrergic NANC responses, although it did inhibit relaxation responses elicited by exogenous VIP, PACAP-27, PACAP-38, PHM, PHV, helospectin-I or -II. K(+) channel inhibitors apamin (1 microM) or charybdotoxin (100 nM) when used alone or in conjunction did not affect non-nitrergic NANC responses. The non-nitrergic NANC responses were not associated with any increase in intracellular cyclic adenosine-3', 5'-monophosphate (cyclic AMP) or cyclic guanosine-3', 5'-monophosphate (cyclic GMP) concentrations. The peptide-induced relaxations were all associated with increases in cyclic AMP concentrations. These results suggest that a neuronal factor elicits non-nitrergic NANC responses in the rabbit vaginal wall. The identity of this factor remains to be established.
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PMID:Characterization of the non-nitrergic NANC relaxation responses in the rabbit vaginal wall. 1181 90

The retinohypothalamic tract (RHT) is a monosynaptic retinofugal pathway mediating information concerning the light/dark cycle from the retina to the brain's biological clock located in the suprachiasmatic nucleus (SCN). Light information, which daily adjusts (entrains) the rhythms of behaviour and physiology generated by the SCN, is mediated by two neurotransmitters, viz. glutamate and pituitary adenylate cyclase activating polypeptide (PACAP), co-stored in the RHT. Substance P (SP) modulates photic- and glutamate-induced phase shifts but data on its possible presence in the RHT are conflicting. By labelling the RHT projection in the SCN with the anterograde tracer cholera toxin subunit B (ChB) and antibodies against PACAP, we have shown that SP immunoreaction is absent from the PACAP/ChB-labelled nerve fibres in the SCN, indicating that the SP-immunoreactive nerve fibres are not part of the RHT but may originate from SP-immunoreactive cell bodies located within the SCN. In the retina, SP immunoreactivity occurs in amacrine cells in the inner nuclear cell layer, in a few displaced amacrine cells in the ganglion cell layer and in a dense plexus of SP-immunoreactive nerve terminals of the inner plexiform layer. Double immunostaining has revealed that SP-immunoreactive cells and fibres in the retina are not identical with the PACAP-immunoreactive ganglion cells that constitute the RHT. These findings together with the demonstration that bilateral eye enucleation does not decrease the number of SP-immunoreactive nerve fibres in the SCN indicate that SP is not a neurotransmitter in the RHT but could be an intrinsic neurotransmitter of the SCN modulating photic input to the clock.
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PMID:Immunoreactive substance P is not part of the retinohypothalamic tract in the rat. 1217 89

The distribution and regional variation of nerves immunoreactive for the neuropeptides pituitary adenylate cyclase activating polypeptide (PACAP), calcitonin gene-related peptide (CGRP), substance P (SP) and vasoactive intestinal polypeptide were investigated in the urinary bladder and distal ureter of young adult (3 months) and aged (24 months) male Wistar rats by indirect immunohistochemistry. Semi-quantitative estimations of nerve densities were made of peptidergic fibres innervating the dome, body and base of the urinary bladder and distal ureter. Sensory innervation of the dome was very sparse and the overall density of innervation increased progressively towards the base of the bladder. The density of innervation in the aged rats was closely comparable to that in the young adults, with the exception of slight reductions in CGRP and SP innervation of the muscle layer. Moreover, there was a marked reduction in the density of PACAP innervation of the subepithelial plexus and of the muscle layer of the bladder base. However, radioimmunoassay showed no significant difference (P>0.05) in PACAP contents between young and aged rat urinary bladder. In the distal ureter of aged rats the densities of innervation by fibres immunoreactive for SP and PACAP but not CGRP were reduced. These findings suggest that the level of sensory innervation of the bladder and distal ureter are reduced in old age and that the afferent limb of voiding reflexes may in consequence be perturbed.
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PMID:Distribution and regional variation of pituitary adenylate cyclase activating polypeptide and other neuropeptides in the rat urinary bladder and ureter: effects of age. 1220 43

Reptiles, including the Burmese python, Python molurus bivittatus, that feed at infrequent intervals show a prominent increase in gastrointestinal mass, metabolism and brush border transport rates after feeding. Current knowledge and theories around these phenomena, as well as studies on the innervation of the reptilian gut, are summarised in this review. Little is known about the putative changes in the nervous and humoral control systems of the gut, and it is not known whether feeding affects innervation and motility of the stomach and intestine. Using immunohistochemistry, we have investigated possible up/down regulation of several neurotransmitters in specimens that had been fasted for a minimum of 3 weeks and specimens that had ingested a large meal 2 days before the experiments were conducted. There were no major changes in the innervation by nerves containing calcitonin gene-related peptide (CGRP), galanin, nitric oxide synthase (NOS), pituitary adenylate cyclase-activating polypeptide (PACAP), somatostatin (SOM), substance P/neurokinin A (SP/NKA), or vasoactive intestinal polypeptide (VIP)-like immunoreactivity. Nor did we find any differences in the effect of substance P (stomach and intestine), galanin (intestine), or bradykinin (intestine) on motility in strip preparations from the gut wall. A significant increase in dry weight of the intestine was obtained 48 h after feeding. We conclude that although there are considerable changes in gut thickness and absorptive properties after feeding, the smooth muscle and its control appear little affected.
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PMID:Effects of digestive status on the reptilian gut. 1244 9

The present review examines various aspects of the developmental expression of neuropeptides and of their receptors in mammalian retinas, emphasizing their possible roles in retinal maturation. Different peptidergic systems have been investigated with some detail during retinal development, including substance P (SP), somatostatin (SRIF), vasoactive intestinal polypeptide (VIP), pituitary adenylate cyclase-activating polypeptide (PACAP), neuropeptide Y (NPY), opioid peptides and corticotrophin-releasing factor (CRF). Overall, the developmental expression of most peptides is characterized by early appearance, transient features and achievement of the mature pattern at the time of eye opening. Concerning possible developmental actions of neuropeptides, recent studies imply a role of SP in the modulation of cholinergic neurotransmission in early postnatal rabbit retinas, when cholinergic cells participate in the retinal spontaneous waves of activity. In addition, the presence of transient SRIF expressing ganglion cells and recent observations in SRIF receptor knock-out mice indicate variegated roles of this peptide in the development of the retina and of retinofugal projections. Furthermore, VIP and PACAP exert protective and growth-promoting actions that may sustain retinal neurons during their development, and opioid peptides may control cell proliferation in the developing retina. Finally, a peak in the expression of certain peptides, including VIP, NPY and CRF, is present around the time of eye opening, when the retina begins the analysis of structured visual information, suggesting important roles of these peptides during this delicate phase of retinal development. In summary, although the physiological actions of peptides during retinal development are far from being clarified, the data reviewed herein indicate promising perspectives in this field of study.
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PMID:Expression of neuropeptides and their receptors in the developing retina of mammals. 1297 90

Nerves have been identified in bone. Their function has recently become the focus of intense study. Metabolic control of bone is influenced by the nervous system. Potential transmitters of this influence include glutamate, calcitonin gene-related protein (CGRP), substance P, vasoactive intestinal peptide (VIP), pituitary adenylate cyclase activating polypeptide (PACAP), leptin, and catecholamines. Disorders of nerves - central or peripheral--can have substantial influence on bone health and repair. Specifically considered are the potential neural influences at work in such conditions as osteoporosis, fracture healing, Charcot osteoarthropathy, musculoskeletal pain syndromes, heterotopic ossification, skeletal growth and development, and obesity-related increased bone density. In this article, we review the current state of experimental and clinical evidence implicating the role of nervous tissue in regulating bone biology and discuss the current understanding of molecular signaling between nervous and osseus tissue in the homeostatic maintenance of the skeleton.
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PMID:Bone and brain: a review of neural, hormonal, and musculoskeletal connections. 1529 19

Using digital motion analysis, the ontogeny of the cholinergic, tachykinin and pituitary adenylate cyclase-activating polypeptide (PACAP) control systems was studied in zebrafish Danio rerio larvae, in vivo. For the first time we show that the regular propagating anterograde waves that occur in the zebrafish larval gut before and around the onset [at 5-6 days post fertilization (d.p.f.)] of feeding are modulated by acetylcholine or atropine, PACAP and NKA (neurokinin A). At 3 d.p.f., when no spontaneous motility has developed, application of acetylcholine did not affect the gut. However, at 4 d.p.f., acetylcholine increased and atropine reduced the frequency of propagating anterograde waves. At 5 d.p.f., NKA increased and PACAP reduced the wave frequency. This suggests that both excitatory and inhibitory pathways develop at an early stage in the gut, independent of exogenous feeding. Immunohistochemistry established the presence of gut neurons expressing PACAP and NKA in the proximal part of the developing gut from the first stage investigated (2 d.p.f.) and before regular motility was observed. 1 d.p.f. (PACAP) or 2 d.p.f. (NKA) stages later the whole gut was innervated. This supports physiological results that gut motility is under neuronal control during the period when regular motility patterns develop.
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PMID:Ontogeny of the gut motility control system in zebrafish Danio rerio embryos and larvae. 1549 54

Pituitary adenylate cyclase-activating polypeptide (PACAP) immunoreactive neural elements have been detected in the mouse spinal cord. The discrepancy of PACAP actions in the role of sensory transmission has been proposed to have potentiation and inhibition on nociceptive responses after intrathecal application of PACAP. The aim of the present study was to assess nociceptive transmission of PACAP in the mouse spinal cord by comparison with that of substance P (SP). The intrathecal injection of PACAP induced licking or scratching behavior similar to that of SP. These PACAP-induced aversive behaviors showed different manner from SP-induced responses in point of time course. SP-induced aversive responses quickly increased and suddenly disappeared almost within 1 min. Meanwhile, following a long latency after the injection, PACAP-induced aversive responses gradually appeared, and then persisted more than 60 min. In the early phase, PACAP produced an increase of tail flick latency. Pretreatment with 6-hydroxydopamine (6-OHDA) which destroys noradrenaline neuron of descending pain inhibitory systems in the spinal cord markedly abridged the latency and augmented the duration of PACAP-induced aversive responses. In this way, PACAP exhibits diverse effects on nociception, such as an analgesic role in early phase of the injection and subsequently lasting algesia. These results suggest that PACAP as a neurotransmitter or neuromodulator might have crucial role in nociceptive transmission system.
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PMID:Diverse effects of intrathecal pituitary adenylate cyclase-activating polypeptide on nociceptive transmission in mice spinal cord. 1551 1

Recent studies have revealed that the pituitary adenylate cyclase-activating polypeptide (PACAP) might act as a psychostimulant. Here we investigated the mechanisms underlying motor hyperactivity in patients with pervasive developmental disorders, such as autism, and attention-deficit hyperactivity disorder (ADHD). We studied the effects of intracisternal administration of 6-hydroxydopamine (6-OHDA) or endocrine disruptors (EDs) on spontaneous motor activity (SMA) and multiple gene expression in neonatal rats. Treatment with 6-OHDA caused significant hyperactivity during the dark phase in rats aged 4-5 weeks. Motor hyperactivities also were observed after treatment with endocrine disruptors, such as bisphenol A, nonylphenol, diethylhexyl phthalate and dibutyl phthalate, during both dark and light phases. Gene-expression profiles produced using cDNA macroarrays of 8-week-old rats with 6-OHDA lesions revealed the altered expression of several classes of gene, including the N-methyl-D-aspartate (NMDA) receptor 1, glutamate/aspartate transporter, gamma-aminobutyric-acid transporter, dopamine transporter 1, D4 receptor, and peptidergic elements such as the galanin receptor, arginine vasopressin receptor, neuropeptide Y and tachykinin 2. The changes in gene expression caused by treatment with endocrine disruptors differed from those induced by 6-OHDA. These results suggest that the mechanisms underlying the induction of motor hyperactivity and/or compensatory changes in young adult rats might differ between 6-OHDA and endocrine disruptors.
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PMID:Motor hyperactivity caused by a deficit in dopaminergic neurons and the effects of endocrine disruptors: a study inspired by the physiological roles of PACAP in the brain. 1551 16

Different peptidergic systems have been investigated with some detail during retinal development, including substance P (SP), vasoactive intestinal polypeptide (VIP), pituitary adenylate cyclase activating polypeptide (PACAP) and somatostatin (SRIF). Concerning possible developmental actions of neuropeptides, VIP and PACAP exert protective and growth-promoting actions that may sustain retinal neurons during their development. In addition, the presence of transient SRIF expressing cells and recent observations in SRIF receptor knock out mice indicate variegated roles of this peptide in the development of the retina and of retinofugal projections. Finally, recent studies have shown that, in the developing rabbit retina, changes in the expression pattern of SP receptors are accompanied by modifications of SP physiological effects, indicating that retinal circuits where SP is involved are likely to function in a substantially different manner before the retina becomes involved in the processing of visual stimuli. SP neurotransmission in the immature retina may subserve developmental events, and SP is likely to represent an important developmental factor for the maturation of retinal neurons and circuitries.
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PMID:Neuropeptides and retinal development. 1609 95


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