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)

Co-localization of mu-opioid receptor (MOR)-like immunoreactivity (-LI) with substance P (SP)-LI, calcitonin gene-related peptide (CGRP)-LI and nitric oxide synthase (NOS)-LI in the nodose, petrosal and jugular ganglia was examined in the rat by a double immunofluorescence histochemical method. About 0.6%, 41% and 95% of neurons with MOR-LI, respectively, in the nodose, petrosal and jugular ganglia showed SP-LI; about 2%, 51% and 66% of MOR-like immunoreactive neurons displayed CGRP-LI in the nodose, petrosal and jugular ganglia, respectively. In addition, about 59% of MOR-like immunoreactive neurons in the nodose ganglia displayed NOS-LI, whereas no NOS-LI was detected in the petrosal or jugular ganglion. These data provide evidence for co-localization of MOR-LI with SP-LI, CGRP-LI and NOS-LI in the vagal and glossopharyngeal afferent neurons, and suggest that MOR may regulate the release of SP, CGRP and nitric oxide from the visceral primary afferent terminals in the nucleus of the solitary tract of the rat.
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PMID:Co-localization of mu-opioid receptor-like immunoreactivity with substance P-LI, calcitonin gene-related peptide-LI and nitric oxide synthase-LI in vagal and glossopharyngeal afferent neurons of the rat. 959 69

Co-expression of mu-opioid receptor-like immunoreactivity (MOR-LI) with substance P (SP)- or calcitonin gene-related (CGRP)-LI was observed in rat trigeminal and dorsal root ganglion neurons. In particular, MOR-LI was found in axon terminals with SP- or CGRP-LI in laminae I and II of the medullary and spinal dorsal horns. MOR may be implicated in modulation of release of SP and CGRP from primary sensory afferents.
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PMID:Immunocytochemical localization of mu-opioid receptor in primary afferent neurons containing substance P or calcitonin gene-related peptide. A light and electron microscope study in the rat. 962 72

The inhibitory effect of inflammation and endotoxins on the secretion of reproductive hormones from the hypothalamo-pituitary axis is well documented. A comparison of the luteinizing hormone (LH) suppressing effects of several pro-inflammatory cytokines revealed that centrally administered IL-1 beta was the most potent inhibitor of pituitary LH secretion; interleukin (IL)-1 alpha and tumor necrosis factor (TNF) alpha were relatively less effective, whereas IL-6 was ineffective. This order of potency suggested that the anti-gonadotropic effects of an immune challenge are most likely attributable to the action of centrally released IL-1 beta, and this was supported by the demonstration that IL-1 beta suppressed hypothalamic luteinizing hormone releasing hormone (LHRH) release. We used a multifaceted approach to identify the afferent signals in the brain that convey immune messages to hypothalamic LHRH neurons. Pharmacological studies with specific antagonists of opioid receptor subtypes demonstrated that activation of the mu 1 receptor subtype was required to transmit the cytokine signal. Furthermore, icv IL-1 beta upregulated hypothalamic POMC mRNA and increased the concentration and release of beta-endorphin, the primary ligand of mu 1 receptors. We have obtained evidence that IL-1 beta also enhanced the gene expression and concentration of tachykinins, a family of nociceptive neuropeptides in the hypothalamus. Blockade of tachykinergic NK2 receptors attenuated IL-1 beta induced inhibition of LH secretion. Collectively, these results demonstrate that IL-1 beta, generated centrally in response to inflammation, upregulates the opioid and tachykinin peptides in the hypothalamus. These two groups of neuropeptides are critically involved in relaying the cytokine signal to neuroendocrine neurons and causing the suppression of hypothalamic LHRH and pituitary LH release.
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PMID:The anti-gonadotropic effects of cytokines: the role of neuropeptides. 978 36

The present study was designed to clarify whether opioid neuronal systems are involved in the beneficial effects of tachykinins such as the neurokinin NK1 receptor agonist, substance P (SP), the neurokinin NK2 receptor agonist, neurokinin A (NKA), and the neurokinin NK3 receptor agonist, senktide, on the scopolamine-induced impairment of spontaneous alternation performance in mice. Intracerebroventricular injections of SP (0.1 microgram), NKA (0.3 microgram) and senktide (3 ng) inhibited the scopolamine (1 mg/kg)-induced impairment of spontaneous alternation performance without influencing total arm entries, indicating the antiamnesic effects of tachykinins. Furthermore, the inhibitory effects of SP, but not those of NKA or senktide, were almost completely reversed by pretreatment with naloxone (1 mg/kg). However, the effects of SP on the scopolamine-induced impairment of spontaneous alternation performance were not influenced by pretreatment with the mu-opioid receptor antagonist, beta-funaltrexamine (5 micrograms), the delta-opioid receptor antagonist, naltrindole (4 ng), and the kappa-opioid receptor antagonist, nor-binaltorphimine (4 micrograms). These findings suggest that the effects of SP, unlike those of NKA or senktide, on the scopolamine-induced impairment of spontaneous alternation performance associated with spatial working memory are not mediated simply via a single type of opioid receptors, such as mu, delta or kappa.
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PMID:Ameliorative effects of tachykinins on scopolamine-induced impairment of spontaneous alternation performance in mice. 981 98

Intrathecal administration of octreotide, a stable somatostatin analogue, provides pain relief in patients, and locally applied somatostatin inhibits firing of nociceptive dorsal horn neurons. In the present study, we have raised polyclonal antibodies that specifically detect the somatostatin receptor sst2A and used these antisera for immunocytochemical localization of the receptor protein in the rat spinal cord and dorsal root ganglia. In the superficial layers of the dorsal horn, sst2A-like immunoreactivity (Li) formed a dense network consisting of neuronal perikarya and dendrites which were often closely apposed by, but not co-contained within, somatostatin-14-immunoreactive nerve fibres and terminals. sst2A-Li was resistant to dorsal rhizotomy and did not colocalize with either substance P or calcitonin gene-related peptide suggesting that sst2A-Li was not located to primary afferents, but rather confined to second-order spinal neurons. The position of sst2A-Li perikarya and dendrites in the dorsal horn appeared to be similar to those containing mu-opioid receptor-Li; however, double labelling experiments revealed no instances of coexistence of these two receptors. sst2A-Li was also observed in the dorsal root ganglia predominantly targeted to the somatic plasmalemma of medium size neurons distinct from those expressing somatostatin-14 or delta-opioid receptors. Thus, the present results not only provide a morphological substrate for spinal octreotide analgesia but also show that somatostatin and opioids are poised to modulate nociceptive transmission by distinct anatomical systems.
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PMID:Immunocytochemical localization of somatostatin receptor sst2A in the rat spinal cord and dorsal root ganglia. 987 49

Evidence is presented that the recently discovered endogenous mu-selective agonist, endomorphin-2, is localized in primary sensory afferents. Endomorphin-2-like immunoreactivity was found to be colocalized in a subset of substance P- and mu opiate receptor-containing fibers in the superficial laminae of the spinal cord and spinal trigeminal nucleus. Disruption of primary sensory afferents by mechanical (deafferentation by dorsal rhizotomy) or chemical (exposure to the primary afferent neurotoxin, capsaicin) methods virtually abolished endomorphin-2-like immunoreactivity in the dorsal horn. These results indicate that endomorphin-2 is present in primary afferent fibers where it can serve as the endogenous ligand for pre- and postsynaptic mu receptors and as a major modulator of pain perception.
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PMID:Endomorphin-2 is an endogenous opioid in primary sensory afferent fibers. 988 85

The liberation of calcitonin gene-related peptide from rat skin in vitro induced by antidromic electrical stimulation of unmyelinated units is demonstrated. Prostaglandin E2 was released concomitantly during C-fiber stimulation. A dose-dependent increase in prostaglandin E2 content of the eluate was also observed in response to stimulation with substance P (10(-7) to 10(-5) M) and calcitonin gene-related peptide (10(-6) and 10(-5) M). In contrast, prostaglandin E2 did not induce measurable release of neuropeptides. The amount of calcitonin gene-related peptide released during suprathreshold electrical stimulation increased with pulse frequency. Calcitonin gene-related peptide and prostaglandin release were completely inhibited in the presence of EMD 61753, a selective kappa-opioid receptor agonist. No significant release of substance P was observed. The data demonstrate a primary release of calcitonin gene-related peptide from unmyelinated but not myelinated primary afferents in the rat skin, which is accompanied by a secondary liberation of prostaglandin E2, connecting neurogenic inflammation to general mechanisms of inflammation.
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PMID:Calcitonin gene-related peptide and prostaglandin E2 but not substance P release induced by antidromic nerve stimulation from rat skin in vitro. 1005 Dec 37

Dynorphin A-(1-17) has been found to produce spinal antianalgesia and allodynia. Thus, we studied whether dynorphin A-(1-17) modulates substance P release evoked by the C-fiber-selective stimulant capsaicin (1 microM) from trigeminal nucleus caudalis slices. Very low concentrations of dynorphin A-(1-17) (0.01-0.1 nM) strongly facilitated capsaicin-evoked substance P release. This dynorphin A-(1-17) effect was not blocked by the opioid receptor antagonists naloxone (100 nM), beta-funaltrexamine (20 nM), naloxonazine (1 nM), nor-binaltorphimine (3 nM) and ICI 174,864 (N,N-dialyl-Tyr-Aib-Phe-Leu; 0.3 microM). Yet, the effect of dynorphin A-(1-17) was blocked by the NMDA receptor antagonist MK-801 ((+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d] cyclohepten-5-10-imine maleate; 0.3 microM). Neonatal treatment with capsaicin (50 mg/kg s.c.), which destroys substance P-containing primary afferents, abolished the excitatory effect of dynorphin A-(1-17) on K+-evoked substance P release. In conclusion, dynorphin A-(1-17) increases substance P release from C-fibers by the activation of NMDA receptors which supports the involvement of presynaptic mechanisms in dynorphin-induced antianalgesia and allodynia.
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PMID:Dynorphin A increases substance P release from trigeminal primary afferent C-fibers. 1006 48

Itching reflects a distinct quality of cutaneous nociception elicited by chemical or other stimuli to neuronal receptors at the superficial layers of the skin and muco-cutaneous orifices. Although recent experimental studies of the conduction and perception of itch have yielded deeper insight into the physiology of this sensory quality, little is known about the neuromechanisms involved in pruritus accompanying many inflammatory skin diseases, in particular, in atopic eczema. Previous case-control studies of our research group with patients suffering from atopic eczema (AE) revealed significantly diminished itch perception after iontophoretic application of different doses of histamine as well as substance P (i.c. injected). Further experiments using acetylcholine (ACh, i.c.) clearly demonstrated that ACh elicits pruritus instead of pain in patients with AE. The first part of the present review deals with the results of our most recent case-control studies on histamine-induced itch perception in atopics devoid of eczema as well as in patients with urticaria or psoriasis compared to atopics with or without manifest eczema. We demonstrated that both focal itch and perifocal alloknesis (i.e., itch elicited by a slight mechanical, otherwise non-itching stimulus) were significantly reduced in eczema-free atopics yet were normal in non-atopics suffering from urticaria or psoriasis. In further studies using ACh i.c. injected into the uninvolved skin of patients with AE, lichen ruber, psoriasis, type IV contact eczema, or non-specific nummular eczema (n = 10/each group), all the atopics and 6/10 psoriatics felt itch instead of burning pain, but none of the others did. Different doses of vasoactive intestinal peptide (VIP) i.c. applied to the controls and the atopics with or without eczema did not markedly increase the intensity of nociceptive sensations. However, ACh induced pain in the controls, pure pruritus in the atopics with acute eczema, and a 'mixture' of pain and itch in the atopics just free from eczema. Obviously, the quality of sensations evoked by ACh and VIP depends on the inflammatory or non-inflammatory state of the atopic skin. In a placebo-controlled, double blind study on histamine-induced focal itch and alloknesis with healthy subjects (n = 15) using naltrexone (opioid receptor antagonist) and cetirizine (H1-blocking agent), naltrexone was found to significantly reduce both itching and alloknesis. Cetirizine reduced focal itch but failed to influence the alloknesis phenomenon. The wheal and flare reaction was suppressed only by cetirizine. These different effects point to a mainly CNS-based activity of naltrexone but a peripheral level effect of cetirizine. Due to long-lasting experience with group sport as a supporting adjuvant for inpatients with AE, we evaluated, by clinical, psychometric, and physiological studies, the therapeutic efficacy of controlled physical exercise in addition to otherwise equal anti-eczematous therapy for both voluntary participants and non-participants in sports by performing several case-control studies, one followed-up to 6 months after the patients' discharge from the hospital. Regular moderate exercises neither deteriorated nor impeded the recovery from AE, ameliorated the participants' scratch controlling ability and significantly their depressed emotional mood. The non-participants failed to achieve these aims. Sweating-induced itch was inhibited in almost all participants if simple skin care (clearing by warm shower, ointment) and short-term rest were used by informed patients. In conclusion, there are several indications that itching is elicited in individuals inclined to cutaneous atopy, regardless of their eczematous or just eczema-free state, by a different physiological pathway from that in non-atopic individuals. Therefore, antipruritic agents influencing the centrally altered nociception of atopics are needed and may be expected in near future. (ABSTRACT TRUNCATED)
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PMID:Recent studies of cutaneous nociception in atopic and non-atopic subjects. 1009 77

Sendide, a tachykinin NK1 receptor antagonist, was tested for antagonism against scratching, biting and licking responses elicited by intrathecal (i.t.) injections of various tachykinin receptor agonists, N-methyl-D-aspartate (NMDA), somatostatin and bombesin, in mice. Tachykinin NK1 receptor agonists, substance P, physalaemin and septide, produced a characteristic behavioural response, consisting of scratching, biting and licking. The substance P-induced response was reduced by small doses (0.0625-1.0 pmol) of sendide in a dose-dependent manner. The behavioural response elicited by other tachykinin NK1 receptor agonists, physalaemin and septide, was also reduced significantly by a small dose (1.0 pmol) of sendide. The inhibitory effect of sendide (1.0 pmol) was not affected by pretreatment with the opioid receptor antagonist, naloxone, at doses up to 4.0 mg/kg. Higher doses of sendide were needed to reduce the behavioural response to neurokinin A, a tachykinin NK2 receptor agonist, neurokinin B, a tachykinin NK3 receptor agonist and eledoisin, a tachykinin NK2/NK3 receptor agonist. Pretreatment with naloxone (2.0 mg/kg, i.p.) significantly antagonized sendide (1024 pmol)-induced inhibition of the behavioural responses to neurokinin A, neurokinin B and eledoisin. The behaviours elicited by i.t. injection of NMDA, somatostatin or bombesin were also reduced by a higher dose (1024 pmol) of sendide and this sendide effect was reversed by naloxone. These findings suggest that sendide at higher doses may possess opioid activity in addition to an antagonistic action at tachykinin NK1 receptors in the spinal cord.
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PMID:Opioid activity of sendide, a tachykinin NK1 receptor antagonist. 1022 61


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