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)

It has been shown previously that microinjection with substance P into the ventral tegmental area of the rat produces an increase in locomotor activity that is dependent upon an intact mesolimbic dopamine (DA) system. In this study substance P was microinjected into subnuclei of the ventromedial mesencephalon and an increase in motor activity was observed in all nuclei corresponding to the A-10 dopamine region. Following behavioral measurements, rats were given substance P and levels of DA and its metabolites measured in the nucleus accumbens. In contrast with the behavioral response, an increase in DA metabolites was observed only after injection made into the nucleus paranigralis or nucleus parabrachialis pigmentosus. Injections made along the midline (nucleus linearis and nucleus interfascicularis) did not elevate DA metabolites in the nucleus accumbens.
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PMID:Substance P modulation of the mesolimbic dopamine system. 241 55

The effects of intraperitoneally or intracerebrally (DA A-10 area) administered substance P (SP) on locomotor activity of rats were studied in an exact 12-h light/12-h dark cycle changing from dark to light at 6 a.m. SP was administered either at 11 a.m. (light phase, minimal locomotor activity) or at 7 p.m. (dark phase, maximal locomotor activity). The effects of 12.5 micrograms/kg SP intracerebral and 125 micrograms/kg SP intraperitoneal were very similar. In the light phase SP produces excitation but inhibition of locomotion in darkness. Hence, the effect of SP depends on the internal mechanisms controlling motor activity and tends to level off the spontaneous circadian oscillation. We found a long lasting SP effect during both the light and dark period. The present experiments led us to the conclusion that SP has a levelling effect on locomotor activity. Probably this effect might be explained as SP's action on the dopaminergic pathway or dopamine metabolism, because the dopamine content in neurons also has a circadian rhythm.
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PMID:Modulation of locomotor activity by substance P in rats. 619 Jan 98

A neutral endopeptidase (NEP) from Lactococcus lactis has recently been cloned and shown to contain high sequence homology with the human neutral endopeptidase, endopeptidase 24.11 (I. Mierau et al., J. Bacteriol. 175, 2087-2096, 1993). The gene for the neutral endopeptidase from L. lactis was cloned into the pQE expression vector, resulting in the fusion of a hexahistidine at the N-terminus. The recombinant enzyme was expressed to high levels in Escherichia coli (approximately 10 mg/liter of culture) and purified to homogeneity in a two-step procedure. A number of peptides were studied as substrates for the enzyme. The enzyme cleaves the following peptides at the Gly3-Phe4 bond: enkephalins, dynorphins A-6, A-8, A-9, A-10, A-13, and A-17, and alpha-neo-endorphin. In addition the enzyme hydrolyzes bradykinin, substance P, beta-endorphin, ACTH, and VIP. Although the cleavage patterns observed are similar to that seen with mammalian neutral endopeptidase, the lactococcal enzyme more efficiently cleaves larger peptide substrates. As observed with the mammalian neutral endopeptidase, the lactococcal enzyme exhibits higher kcat/K(m) values for the enkephalins than for their corresponding amides, indicating the functionality of an active-site arginine. Inactivation of the lactococcal endopeptidase by diethyl pyrocarbonate and protection afforded by the substrate dynorphin A-6 indicate the functionality of a positionally conserved active-site histidine. This was confirmed by demonstrating that conversion of this histidine, histidine 587, to glutamine generated inactive enzyme. Similarly, conversion of the putative zinc ligand glutamate 535 to glutamine led to inactive enzyme. These studies indicate a conservation of critical catalytic residues between the two enzymes and suggest that the lactococcal endopeptidase is a better model than thermolysin for the mammalian enzyme.
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PMID:Heterologous expression and characterization of recombinant Lactococcus lactis neutral endopeptidase (neprilysin). 880 62

Excessive grooming behaviour is induced by intracerebroventricular injections of the neuropeptide glutamic acid isoleucine amide (neuropeptide-EI), via the activation of A-10 dopaminergic neurons and the noradrenergic system. Our object was to study the latter system involved in these behaviours, using male Wistar rats weighing 250-300 g with i.c.v. implants. The results show that all the adrenoceptor antagonists "per se" do not affect excessive grooming behaviour or motor activity. Intracerebroventricular administration of propranolol, a general beta-adrenoceptor antagonist, before neuropeptide-EI, inhibited the induced excessive grooming behaviour in a dose dependent manner. Metoprolol, a beta(1)-adrenoceptor antagonist, also blocked this behaviour. However, intracerebroventricular injections of phentolamine, an alpha-adrenoceptor antagonist, and ((+/-)-1-[2,3-(Dihydro-7-methyl-1H-inden-4-yl)oxy]-3-[(1-methylethyl)amino]-2-butanol), a beta(2)-adrenoceptor antagonist, had no effect on the behaviour induced by neuropeptide-EI induced behaviour for any of the doses tested. On the other hand, isoproterenol, a general beta-adrenoceptor agonist and dobutamine, a beta(1)-adrenoceptor agonist, both elicited similar behaviours as those induced by neuropeptide-EI. These results support the hypothesis that a relationship exists between neuropeptide-EI and beta-adrenoceptors, more specifically the beta(1)-adrenoceptor, as found with other similar endogenous peptides such as neurotensin, cholecystin, substance P and alpha-melanocyte stimulating hormone. Hence, neuropeptide-EI could probably be exerting a neuromodulating effect on the central nervous system.
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PMID:Effect of beta-adrenoceptors on the behaviour induced by the neuropeptide glutamic acid isoleucine amide. 1753 27