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)

Systematic analysis of the hydrolysis of benzyloxycarbonyl (Cbz)-dipeptides by cathepsin A [EC 3.4.12.1] purified from rat liver lysosomes showed that multiple forms of cathepsin A preferentially cleave peptide bonds with leucine, methionine, and phenylalanine. Cbz-Met-Met, -Met-Phe, -Phe-Met, and -Phe-Ala were hydrolyzed 6 to 8 times faster than the standard substrates, Cbz-Glu-Phe and Cbz-Glu-Tyr. The pH optima of the hydrolyses were 4.6 to 5.8. Hydrolysis of peptide bonds with glycine, isoleucine, and proline was very slow, but the rate depended on the nature of the adjacent amino acids. Proteins such as albumin, cytochrome c, gamma-globulin, hemoglobin, histone, myoglobin, and myosin were scarecely degraded. Peptide hormones, such as glucagon and adrenocorticotropic hormone (ACTH) were hydrolyzed markedly with optimum pH's of 4.5 and 4.6, respectively. Angiotensin I, II, bradykinin, Lys- and Met-Lysbradykinin (kallidin and Met-kallidin), and substance P were also hydrolyzed at appreciable rates. pH optima for these peptide hormones were 5.2 to 5.6. On the other hand, insulin and its A chain, luteinizing hormone-releasing hormone (LH-RH), oxytocin and vasopressin were cleaved slowly. In the hydrolyses of glucagon and other peptides, multiple forms of rat liver lysosomal cathepsin A again showed a carboxypeptidase nature, cleaving peptide bonds sequentially from the carboxyl terminal. Almost all of the amino acids were cleaved on prolonged incubation. Vaso-activites of angiotensin II and bradykinin were rapidly lost on hydrolysis by cathepsin A. Lysosomal cathepsin C [dipeptidylaminopeptidase I, EC 3.4.14.1] also activated angiotensin II, but did not inactive bradykinin. Cathepsin A, therefore, can be regarded as one of the lysosomal angiotensinases and kinases. No distinct differences were observed between the multiple forms of cathepsin A in these hydrolyses and inactivations of peptides.
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PMID:Studies on cathepsins of rat liver lysosomes. III. Hydrolysis of peptides, and inactivation of angiotensin and bradykinin by cathepsin A. 1 61

The effects of various neurogenic peptides and neurotransmitter substances on the release of ACTH induced by hypothalamic corticotropin releasing factor (HY-CRF) were investigated using monolayer cultured anterior pituitary cells. Test substances were given in combination with 0.05-0.1 hypothalamic extract (HE)/ml, because HE evoked a significant ACTH release and a linear dose response relationship was demonstrated sequentially between 0.0165 HE/ml and 0.5 HE/ml. Relative high doses of lysine-vasopressin showed a slight additive effect on the release of ACTH induced by 0.1 HE/ml. Leu-enkephalin, dopamine, prostaglandin E1 and E2 slightly reduced the release of ACTH induced by HY-CRF, but the inhibitory effect of these substances were not dose-related. Other tested substances including luteinizing hormone releasing hormone, thyrotropin releasing hormone, somatostatin, melanocyte stimulating hormone release inhibiting factor, beta-endorphin, neurotensin, substance P, vasoactive intestinal polypeptide, angiotensin II, norepinephrine, serotonin, acetylcholine, histamine and gamma-amino butyric acid showed neither agonistic nor antagonistic effect on the release of ACTH induced by HY-CRF. These results indicate that the release of ACTH is controlled specifically by HY-CRF and corticosterone, and modified slightly by some other substances such as vasopressin and prostaglandins, and that the effect of most other neurogenic peptides and neurotransmitter substances is negligible or non-physiological at the pituitary level.
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PMID:ACTH release in pituitary cell cultures. Effect of neurogenic peptides and neurotransmitter substances on ACTH release induced by hypothalamic corticotropin releasing factor (CRF). 3 43

Biologically active peptides and neurotransmitter substances were added to anterior pituitary cell cultures to examine the presence of corticotropin releasing factor (CRF)-like activity. Hypothalamic extract (HE) induced significant dose-related increase of ACTH, and the lowest effective dose was 0.01 HE/ml. Other tested substances including luteinizing hormone-releasing hormone, thyrotropin releasing hormone, melanocyte stimulating hormone release inhibiting factor, somatostatin, substance P, neurotensin, beta-endorphin. leu-enkephalin, met-enkephalin, bradykinin, norepinephrine, dopamine, serotonin, acetylcholine, histamine, gamma-amino butyric acid or gamma-hydroxy butyric acid showed no CRF-like activity. Relatively high doses of lysine vasopressin, arginine vasopressin and angiotensin II increased the release of ACTH in pituitary cell cultures, but the maximal ACTH response was markedly less than with HE. These results indicate that cultured anterior pituitary cells are sensitive and fairly specific in detecting CRF(s) comparing with other detecting procedures.
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PMID:Specificity of cultured anterior pituitary cells in detecting corticotropin releasing factor(s): the effect of biologically active peptides and neurotransmitter substances on ACTH release in pituitary cell cultures. 3 34

1. Dispersed rat parotid acinar cells were used to study the effects of secretagogues on 22Na uptake. 2. Carbachol stimulated 22Na uptake, and caused a net gain in total Na and a loss in total K. These effects were accentuated in the presence of 10(-3) M-ouabain. 3. Substance P, epinephrine and phenylephrine also stimulated 22Na uptake while isoproterenol and angiotensin II did not. 4. The 22Na uptake due to carbachol was inhibited by atropine, procaine or CoCl2; the response to Substance P was inhibited by CoCl2 only. 5. Extracellular Ca was required for stimulation of 22Na uptake by carbachol. Strontium but not Ba could substitute for Ca in supporting 22Na uptake. 6. Uptake of 22Na was stimulated by the divalent cationophore, A-23187, and Ca was required for this effect. 7. It is concluded that activation of Ca influx by muscarinic, alpha-adrenergic or peptide agonists triggers, among other effects, an increased membrane permeability to Na.
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PMID:Calcium and receptor regulation of radiosodium uptake by dispersed rat parotid acinar cells. 9 91

An enzyme which catalyzes the deamidation of thyroliberin (TRF; less than Glu-His-Pro-NH2) has been purified 110-fold from extracts of bovine anterior pituitary by ammonium sulfate fractionation, ion exchange chromatography on DEAE-cellulose, and gel filtration. This enzyme of 76,000 molecular weight (as estimated by gel filtration) exhibits maximal activity at neutral pH (optimum pH 7.4 to 7.6) in buffers of high ionic strength supplemented with thiol-protecting agents. As indicated by the strong inhibition of the enzymatic activity by N-ethylmaleimide and Hg2+, as well as by the extreme sensitivity toward diisopropyl fluorophosphate, -SH, and -OH residues apparently represent essential functional groups of the enzyme. The stereospecific deamidation of TRF (Km = 4.1 . 10(-4) M) is inhibited competitively by TRF analogues which contain proline or by the proline containing biologically active peptides luliberin (LH-RF), oxytocin, vasopressin, angiotensin II, and Substance P. TRF analogues without proline or peptide amides without proline are ineffective. This enzyme cleaves the appropriate Pro-X bonds in luliberin, angiotensin II, pyroGlu-His-Pro-Gly-NH2, and the collagenase substrate Z-Gly-Pro-Leu-Gly-Pro. Thus, it may be characterized as a post-proline-cleaving enzyme.
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PMID:Characterization of "thyroliberin-deamidating enzyme" as a post-proline-cleaving enzyme. Partial purification and enzyme-chemical analysis of the enzyme from anterior pituitary tissue. 11 64

Substance P stimulation of salivation in rats has been studied as has its in vitro enhancement of amylase release by isolated parotid cells. The extent of the stimulation on amylase release by isolated parotid cells was dependent upon the concentration of substance P, with the minimum effective concentration being 1 nM. The substance P effect was detectable within 1 min after incubation and lasted for at least 50 min. Substance P stimulation was demonstrable at 25--37 degrees C but not at 0 degrees C. Adrenocorticotropic hormone (ACTH), thyrotropin-releasing hormone (TRH), vasopressin and neurotensin had no effect on amylase release. These results suggest that substance P may act directly on the parotid cells. Examination of the salivary-stimulating activity of fragments of substance P showed that the C-terminal octapeptide and (pyroglutamyl)hexapeptide were active, although less potent than substance P, whereas its free acid, C-terminal tetra- and tri-peptides were inactive. Vasopressin, angiotensin II and neurotensin could inhibit substance P induced salivation, whereas TRH, ACTH and somatostatin had no effect. Amylase activity per unit volume of saliva was not changed by the injection of vasopressin, angiotensin II or neurotensin. These vasoactive peptides did not affect substance P stimulation of amylase release by isolated parotid cells. The results indicate that vasopressin, angiotensin II and neurotensin inhibit the action of substance P on salivation at sites other than the parotid cells.
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PMID:Substance P stimulation of amylase release by isolated parotid cells and inhibition of substance P induction of salivation by vasoactive peptides. 22 41

The ability of the angiotensin antagonists 1-Sar,8-Ala-angiotensin II (saralasin) and 1-Sar,8-Leu-angiotensin II (sarleusin) and the bradykinin-potentiating peptide B (BPP) to modify the twitch-enhancing effect of angiotensin II, bradykinin, and substance P, was studied in the isolated field-stimulated guinea-pig vas deferens. The twitch-enhancing effect of angiotensin, bradykinin and substance P underwent tachyphylaxis which was strongest after angiotensin. Saralasin and sarleusin were without influence on the twitch response and antagonized the effect of angiotensin, but not that of bradykinin or substance P, respectively. The features of the antagonism to angiotensin were compatible with the notion that saralasin is a competitive and sarleusin a dual antagonist. BPP did modify either the twitch response or the effects of angiotensin, bradykinin, and substance P. In the non-stimulate vas, the contracting effect of noradrenaline did not undergo tachyphylaxis and was not mofified by angiotensin, bradykinin, or substance P. It is concluded that there exist in the guinea-pig vas specific peptide receptors, one of them having the properties of a "typical" angiotensin receptor.
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PMID:An attempt to differentiate the effects of angiotensin II, substance P and bradykinin on the field-stimulated guinea-pig vas deferens. 46 11

The activity and distribution of substance P-catabolizing enzyme(s) were studied in the rat kidney. Kidney homogenates inactive substance P 5-20 times as fast as do homogenates of intestine, liver, lung, heart or brain. The catabolizing activity was highest in the cortex and decreased progressively down the papilla. Cortex of rat kidney was homogenized and fractions enriched in microsomal membrane, final supernatant, plasma membrane, endoplasmic reticulum, brush border and intact glomeruli were prepared. The identity and homogeneity of the preparations were determined by assaying marker enzymes and by morphological examination. Substance P was catabolized most rapidly by the microsomal and plasma-membrane-enriched fractions, and least rapidly by endoplasmic reticulum or final supernatant fractions. Purified brush border of proximal tubules inactivated substance P more than 10 times as fast as isolated glomeruli. Our experiments show that substance P is catabolized at a rate that is similar to the rates of inactivation of bradykinin and angiotensin II. Further, the distribution of substance P-catabolizing activity in various kidney fractions is similar to the distribution of kininase and angiotensinase activities previously reported.
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PMID:Renal inactivation of substance P in the rat. 64 14

The undecapeptide eledoisin caused vigorous and copious drinking within a minute or two of injection into the pigeon forebrain. Systemic injections of the same doses were ineffective. The relative efficacy of eledoisin and angiotensin II as dipsogens in the pigeon was similar to that of carbachol and angiotensin II in the rat. The related peptides eledoisin hexapeptide, physalaemin and substance P also caused some drinking, but they were less effective than eledoisin. In the rat none of these substances caused drinking. On the contrary eledoisin and substance P were found to depress angiotensin-induced drinking, but carbachol-induced drinking was not depressed to the same extent by these peptides. The preferential depression of angiotensin II-induced drinking resembles the effects of other vasoplegic drugs on this response in the rat, and may be related to the potent vasodilator properties of these peptides.
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PMID:Eledoisin, substance P and related peptides: intracranial dipsogens in the pigeon and antidipsogens in the rat. 67 89

Sodium excretion is correlated with kallikrein excretion in man, rabbits and rats on a free sodium and water intake, but not on a constant sodium or constant water intake. The correlation also exists during arterial infusion of angiotensin II, substance P and various vasodilators. During sodium depletion, the stimulation of the renin-angiotensin system causes increased drinking in rats and rabbits. The high angiotensin levels would stimulate kallikrein excretion. The excretion of water and dilution of urine are facilitated by the renal kallikrein-kinin system, even when antidiuretic hormone is high. This negative correlation between urinary osmolality and kallikrein excretion exists during arterial infusion of angiotensin or substance P and various vasodilators. During renal artery constriction, the kallikrein release per minute decreases, but over successive 10-minute periods, the kallikrein concentration in urine rises. This rise is correlated with some recovery in the clearance of rho-aminohippurate and inulin. Since kallikrein is released into renal lymph during saline infusion at a rate that correlates with its release into the urine, it is suggested that the renal kallikrein-kinin system protects the renal vasculature against the constricting action of the renin-angiotensin system. The decreased release of kallikrein (via the lymphatics into the circulation) during renal artery constriction, or decreased renal compliance, would potentiate the hypertensive effect of these procedures which cause increased renin release.
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PMID:The renal kallikrein-kinin system and the regulation of salt and water excretion. 76 62


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