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)

The pharmacological specificity of the GABA agonist muscimol-induced contralateral turning behavior after unilateral injection into substantia nigra pars reticulata (SNR) has been studied. Muscimol-induced turning was antagonized by intranigral bicuculline methochloride (BMC) and picrotoxin, whereas antagonists of glycine, morphine, dopamine, noradrenaline, and serotonin were ineffective. Glycine induced a qualitatively similar turning behavior which was strychnine-sensitive but relatively BMC and picrotoxin-insensitive. Other drugs, including substance P, kainic acid, clonidine, oxymetazoline, serotonin, and carbachol, induced turning that could be dissociated from the effect of muscimol. Muscimol-induced turning was dopamine-independent, indicated by resistance to haloperidol (1 mg/kg), to pretreatment with reserpine (7.5 mg/kg) plus alpha-methyl-p-tyrosine (200 mg/kg), to haloperidol injections into the SNR, striatum and nucleus accumbens, and finally to kainic acid lesions of the striatum. 6-Hydroxydopamine lesions increased the efficacy of intranigral muscimol, while kainic acid lesions of the SNR antagonized muscimol. Muscimol-induced turning was inhibited by oxotremorine (0.25 mg/kg), by intranigral carbachol, and by apomorphine (0.1--0.5 mg/kg), but only moderately by intranigrally injected apomorphine. These data suggest specificity of GABA-agonist-induced contralateral turning and indicate an interaction between nigral GABA and other neurotransmitters, particularly dopamine and acetylcholine.
 ...
PMID:GABAergic and glycinergic mechanisms within the substantia nigra: pharmacological specificity of dopamine-independent contralateral turning behavior and interactions with other neurotransmitters. 3 44

The regulation of neostriatal cholinergic function by tachykinins (TKs) has been studied by measuring endogenous ACh released from rat neostriatal slices. Septide (SEP; a highly selective substance P analog), neurokinin A (NKA), and neurokinin B (NKB) elicited endogenous ACh release in a concentration-dependent manner. The rank order in potency was the following: NKB (EC50 approximately 0.5 nM) greater than NKA (EC50 approximately 7 nM) greater than SEP (EC50 approximately 12 nM). Spantide (SPA) was less effective (39% inhibition) than [D-Arg6, D-Trp7,9, N-Methyl-Phe8]-substance P fragment 6-11 (53% inhibition) at antagonizing ACh release evoked by SEP and NKA. Smaller doses of the antagonists inhibited the effects of SEP compared to NKA, and the effects of NKB could only be antagonized by SPA. These findings suggest the involvement of the three neurokinin (NK) receptors in ACh release evoked by TKs with the following rank order: NK3 greater than NK2 greater than NK1. 6-Hydroxydopamine lesions of nigrostriatal neurons and tetrodotoxin (TTX) intoxication of striatal tissue revealed two different patterns of regulation of cholinergic function by TKs. On the one hand, SEP and NKA evoked ACh release, independently of the nigrostriatal dopaminergic system, by acting on NK1 and NK2 receptors that are probably localized on the somatodendritic field of cholinergic neurons receiving substance P terminals. On the other hand, dopaminergic terminals seem to regulate NKB neurons that modulate cholinergic neurons, because NKB-evoked ACh release decreased by 24% in the denervated striata. In addition, TTX partially blocked (50%) ACh release evoked by NKB, suggesting that NKB acts on NK3 receptors at both the nerve terminals and the somatodendritic field of cholinergic neurons.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Neurokinin receptors differentially mediate endogenous acetylcholine release evoked by tachykinins in the neostriatum. 165 75

The presence and distribution of galanin-immunoreactivity was examined in the uterine cervix and paracervical autonomic ganglia of the female rat. Some animals were treated with capsaicin to determine if galanin-immunoreactivity was present in small-diameter primary afferent nerves. Other animals were treated with the noradrenergic neurotoxin 6-hydroxydopamine to ascertain if galanin-immunoreactivity was present in sympathetic noradrenergic nerves. Galanin-immunoreactive nerve fibers were sparse in the cervical myometrium and vasculature, but numerous in the paracervical ganglion where they appeared to innervate principal neurons. Immunoreactivity was also present in dorsal root ganglia, dorsal horn of spinal cord, and inferior mesenteric ganglia. Capsaicin treatment resulted in a marked reduction of galanin-immunoreactivity in the spinal cord dorsal horn, but not in the dorsal root ganglia, paracervical ganglia, or cervix (although there was a substantial reduction of substance P-, neurokinin A-, and calcitonin gene-related peptide-immunoreactivity in the dorsal horn. dorsal root ganglia, and uterine cervix). 6-Hydroxydopamine treatment did not cause any appreciable change in the galanin-immunoreactivity in any tissues. We conclude that galanin-like immunoreactivity is expressed in nerve fibers innervating the paracervical ganglia and uterine cervix of the female rat. This immunoreactivity is probably present in afferent nerves and could play a role in neuroendocrine reflexes and in reproductive function.
 ...
PMID:Galanin-immunoreactive nerves in the female rat paracervical ganglion and uterine cervix: distribution and reaction to capsaicin. 247 36

The various subpopulations of autonomic and sensory nerves supplying the mammalian cardiovascular system may be demonstrated using specific immunocytochemical and histochemical techniques, but no single marker has previously been available for the visualisation of the entire innervation. Protein gene product (PGP) 9.5 was first identified in extracts of human brain and found to represent a major protein component of the neuronal cytoplasm. We have demonstrated that PGP 9.5 immunoreactivity occurs in the guinea pig cardiovascular innervation and is present in more individual nerve fibres than other general neuronal markers (neuron-specific enolase and neurofilaments). PGP 9.5 immunoreactivity was localized to both intrinsic neurones and nerve fibres in the guinea pig heart. In the vascular system PGP 9.5-immunoreactivity occurred in an extensive plexus of fine perivascular nerve fibres and fascicles running around and along both arteries and veins, mainly at the adventitial-medial border. At the ultrastructural level, this immunoreactive material was localized to the axonal cytoplasm and did not appear to be associated with cytoskeletal elements or secretory vesicles. 6-Hydroxydopamine (6-OHDA) pretreatment resulted in the degeneration of noradrenergic axon terminals containing PGP 9.5, tyrosine hydroxylase (TH) and neuropeptide tyrosine (NPY) immunoreactivities. Most of the perivascular nerve fibres which remained displayed substance P- and calcitonin gene-related peptide (CGRP) immunoreactivity, as well as PGP 9.5 immunoreactivity. Capsaicin pretreatment resulted in a depletion of both substance P and CGRP immunoreactivity, but had no apparent effect on PGP 9.5 immunostaining. In the heart PGP 9.5 immunoreactivity also appeared to be present in presumed postganglionic cholinergic nerves. PGP 9.5 may be a useful marker when examining regional variations in cardiovascular innervation and for determining the relative proportions of nerve subpopulations.
 ...
PMID:The visualisation of cardiovascular innervation in the guinea pig using an antiserum to protein gene product 9.5 (PGP 9.5). 310 56

The effects of lesioning mesostriatal dopamine projections or striatal neurons on tachykinin binding in the basal ganglia were assessed in the rat. 6-Hydroxydopamine lesions of the medial forebrain bundle destroyed striatal dopamine terminals as assessed by [3H]mazindol autoradiography, but did not significantly affect the binding of NK-1 ([3H][Sar9,Met(O2)11]substance P) or NK-3 ([3H]senktide) tachykinin ligands in the striatum. 6-Hydroxydopamine lesions significantly reduced NK-3 binding in the substantia nigra pars compacta, but not the ventral tegmental area. In contrast, striatal quinolinic acid lesions reduced both NK-1 and NK-3 binding in the striatum, but failed to affect NK-3 binding in the substantia nigra. These findings suggest that both NK-1 and NK-3 receptors within the striatum are predominantly post-synaptic with respect to dopamine neurons, whereas nigral NK-3 receptors are located on dopaminergic neurons.
 ...
PMID:Localization of striatal and nigral tachykinin receptors in the rat. 751 61

6-Hydroxydopamine (6-OHDA) stimulates the release of catecholamines from sympathetic nerves. This stimulation has been proposed as the basis of the 6-OHDA-induced increase in vascular permeability in the rat knee joint. We sought to determine whether 6-OHDA increases vascular permeability in the rat trachea through a similar mechanism. We also sought to determine whether sympathetic nerves contribute to the plasma extravasation caused by stimulating sensory nerves with capsaicin. In anesthetized rats, an intratracheal infusion of 6-OHDA caused more Monastral blue extravasation than did an infusion of vehicle (area density, 23 +/- 3% vs. 9 +/- 1%). Chemical sympathectomy, which reduced the number of tyrosine hydroxylase-immunoreactive nerves by 98%, did not reduce the amount of extravasation induced by 6-OHDA. However, pretreatment with capsaicin, which reduced the number of substance P-immunoreactive nerves by 95%, reduced the Monastral blue extravasation induced by 6-OHDA by 98%. Extravasation induced by stimulating sensory nerves with capsaicin was not significantly different in tracheae with or without sympathetic nerves. We conclude that in the rat trachea infusion of 6-OHDA causes plasma extravasation by stimulating sensory nerves, not by stimulating sympathetic nerves. Furthermore, sympathetic nerves are not essential for the plasma extravasation induced by capsaicin.
 ...
PMID:Plasma extravasation induced in rat trachea by 6-OHDA is mediated by sensory nerves, not by sympathetic nerves. 790 98

Perfusion of 6-hydroxydopamine into the rat knee and trachea induces plasma extravasation, possibly by tissue-specific mechanisms involving sympathetic and sensory nerves respectively, and we aimed to identify the mediators which contribute to this response in skin. 6-Hydroxydopamine (both hydrobromide and hydrochloride salts), dose dependently increased plasma extravasation into rat dorsal skin, however, when compared to bradykinin or the tachykinin NK1 receptor agonist GR73632, high concentrations of 6-hydroxydopamine (1-10 mumol/site) were required. The response to 6-hydroxydopamine was not inhibited in chemically sympathectomised rats (6-hydroxydopamine, 300 mg/kg i.p. over 7 days) but was significantly reduced by co-administration with the histamine (H1) and the 5-HT receptor antagonists mepyramine and methysergide and in skin sites pre-injected with compound 48/80 (4 micrograms, -18 h) to degranulate dermal mast cells. The response was not inhibited by co-injection of the tachykinin NK1 receptor antagonist SRI40333 or by the cyclo-oxygenase inhibitor indomethacin (5 mg kg-1 i.p., -30 min) except at the lowest dose of 6-hydroxydopamine (1 mumol/site). We conclude that 6-hydroxydopamine is not a potent or selective mediator of increased vascular permeability in rat skin but, at high concentrations, may induce oedema formation via release of vasoactive amines from mast cells, augmented by generation of prostaglandins.
 ...
PMID:Investigation of 6-hydroxydopamine-induced plasma extravasation in rat skin. 877 59

To investigate the mechanisms underlying motor hyperactivity, we performed intracisternal injection of 6-hydroxydopamine or endocrine disruptors in rats on postnatal day 5. 6-Hydroxydopamine (100 microg, 488 nmol) caused a significant increase in spontaneous motor activities at 4 weeks of age. Gene-expression profiling using a cDNA membrane array revealed alterations in several classes of gene at 8 weeks of age. In the midbrain, gene expression was enhanced in dopamine transporter 1; a platelet-derived growth factor receptor; dopamine receptor D4; galanin receptor 2; arginine vasopressin receptor 2; neuropeptide Y; tachykinin 2; and fibroblast growth factor 10. Expression was also enhanced in the glutamate/aspartate transporter gene in the striatum. Rats received an endocrine disruptor (87 nmol), such as bisphenol A, nonylphenol, p-octylphenol, or diethylhexylphthalate, which also caused motor hyperactivity at 4 weeks. The effects of bisphenol A on motor activity were dose-dependent from 0.87 to 87 nmol. The phenols caused a deficit in dopamine neurons, similarly to the deficit caused by 6-hydroxydopamine. Gene-expression profiles after treatment with endocrine disruptors showed variation and differed from those of 6-hydroxydopamine. The results suggest that neonatal treatment with environmental chemicals can generate an animal model of attention-deficit hyperactivity disorder, in which clinical symptoms are pervasive.
 ...
PMID:Effects of neonatal treatment with 6-hydroxydopamine and endocrine disruptors on motor activity and gene expression in rats. 1530 6