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)

Pain is a complex phenomenon involving both neurophysiological and psychological components. Pathophysiological mechanisms involve neural pathways, and a variety of pain-producing substances and modulating mechanisms. These include acetylcholine, serotonin, histamine, bradykinin, prostaglandins, substance P, somatostatin, cholecystokinin, vasoactive intestinal polypeptide, noradrenaline and endogenous opioid peptides. In assessing patients with pain, it is essential to evaluate the cause of the pain, its severity, type, location, duration, quality, and response to therapies, among other factors. The measurement of pain is dependent on subjective responses, which are evaluated by methods which have been well developed over the last three decades. Alleviation of pain by non-drug treatments must be considered as well as use of pharmacological treatments. These include psychological support, placebos, relaxation training, biofeedback, hypnosis, heat, cold, physical supports and surgery. Oral drugs are generally preferable to parenteral drugs, as are drugs with few side effects and low addictive liability. Both overtreatment and undertreatment are to be avoided. Patients can be expected to differ in their needs and responses, and economic considerations ought not be ignored. Newer approaches to pain management include self-administration of parenteral drugs, the search for new types of analgesics and appreciation of the relationship between age, sex, race, etc. and the response to analgesics. Tricyclic antidepressants, phenothiazines and the new non-steroidal anti-inflammatory drugs have pointed the way to possible improvements in our ability to tailor specific drugs to the needs of individual patients.
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PMID:The management of pain. 355 78

Lingual blood flow and its distribution were determined at rest and in response to local cooling of the tongue (32 degrees C) in 6 anaesthetized, paralyzed and artificially ventilated dogs before and after two intraarterial (i.a.) injections of capsaicin (2.5 mg) at an interval of about 40 min. In 3 dogs, the same protocol was performed after degeneration of the chorda-lingual and glossopharyngeal nerves due to prior transection. In general the first i.a. injection of capsaicin resulted in a marked and the second injection in a smaller decrease of lingual blood flow. Local cooling of the tongue induced significant increases in lingual blood flow before as well as after capsaicin treatment, regardless of whether sensory innervation was intact or degenerated. In both the untreated and capsaicin treated dogs the increase in lingual blood flow during local cooling of the tongue was solely due to an increase in blood flow through the arteriovenous anastomoses, while blood flow through the capillaries of the mucosa and muscles even decreased. The findings suggest that capsaicin-induced vasoconstriction of the tongue vessels is due to a direct effect on vascular receptors. It is further suggested that cold vasodilatation of the canine tongue is not mediated by axon collaterals releasing substance P. Direct thermal effects on the intramural ganglia and the postganglionic vasomotor efferents innervating the AVAs, or on AVAs basal tone itself are suggested as the underlying mechanism.
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PMID:Responsiveness of microcirculation and local cold vasodilation to capsaicin in the intact and chronically denervated canine tongue. 366 Dec 18

Centrally administered neuropeptides were investigated for their effects on the development of gastric lesions in rats. Thyrotropin releasing hormone (TRH), vasoactive intestinal peptide (VIP) and gonadotropin releasing hormone (LHRH) produced gastric lesions acutely, with TRH demonstrating the most pronounced effect in terms of incidence and severity. Ten-fold higher doses of the same peptides administered intravenously produced none or very few gastric lesions. Moreover, pretreatment with atropine partially inhibited their production. Corticotropin releasing factor (CRF) exhibited only mild ulcerogenic effects, and the gastric lesions induced with this peptide developed more slowly than with TRH, VIP and LHRH. Although ulcerogenic in their own right, none of these four neuropeptides significantly potentiated the potent ulcerogenic effects of cold-restraint stress. Since other neuropeptides, including somatostatin, human pancreatic growth hormone releasing factor (hpGRF), substance P, bombesin, and neurotensin, had no demonstrable effects on gastric mucosa, we can conclude that the lesions were not a general effect of intracisternal administration of neuropeptides. The results suggest that within the central nervous system, there are several neuropeptides that play a significant role in the development of gastric lesions via, at least in part, vagal-dependent mechanisms.
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PMID:The effects of centrally administered neuropeptides on the development of gastric lesions in the rat. 392 Apr 62

Bilateral, radio-frequency destruction of the ventro-medial posterior hypothalamus (VMPH) resulted, as compared to sham-operated and control rats and evaluated in the tail-flick and vocalization tests, in a significant decrease in basal nociceptive threshold on day 4 post-surgery. By day 12, however, no significant difference between sham and lesioned rats was seen. At this time the antinociception elicited by either acute foot-shock or cold-water-immersion stress was profoundly attenuated. The antinociceptive response to various doses of morphine was not, in contrast, diminished. As established by use of radioimmunoassay, these lesions did not significantly alter hypothalamic levels of beta-endorphin, met-enkephalin, dynorphin or alpha-neo-endorphin. They did, however, produce a pronounced and significant fall in the hypothalamic content of substance P. These data are indicative that the VMPH may, via a mechanism not involving endorphins, be of importance in the determination of basal nociceptive threshold and in the generation of stress-, but not morphine-, evoked antinociception. The relationship of these findings to the interconnections of the VMPH, and to the possible significance of substance P and the pituitary in nociceptive processes, is discussed.
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PMID:Evidence for a role of the ventro-medial posterior hypothalamus in nociceptive processes in the rat. 613 87

In the rabbit iris sphincter muscle, electrical transmural stimulation produced fast and slow components of contraction which were markedly attenuated by tetrodotoxin. The fast component was augmented by physostigmine and was abolished by atropine, while the slow component was little affected. Adrenergic and ganglionic blocking agents did not inhibit the slow component. Therefore, the fast component is probably cholinergic, while the slow one is noncholinergic, nonadrenergic in nature. Capsaicin did produce a considerable contractile response, but there was a gradual decline with repetitive application and a tachyphylaxis occurred. Under such conditions the slow but not the fast component was abolished. Substance P and acetylcholine produced the largest contraction, while ATP, histamine, serotonin and noradrenaline produced little or no response. In cold stored preparations, the responses to electrical transmural stimulation and capsaicin were either markedly attenuated or abolished, whereas substance P and acetylcholine produced considerable contractions. Baclofen and theophylline did not inhibit the slow response to electrical transmural stimulation or the response to substance P and capsaicin. Thus, electrical transmural stimulation produces cholinergic and noncholinergic, non-adrenergic contractions in the rabbit iris sphincter muscle and the latter response is considered to be mediated by substance P or a related peptide released from the neural component.
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PMID:Noncholinergic, nonadrenergic contraction and substance P in rabbit iris sphincter muscle. 617 63

Various peptides have been shown to alter body temperature. Intraperitoneal administration of substance P (SP) in doses of 25 and 250 micrograms/kg produces a significant hypothermic response in normotensive rats under cold exposure at 4 degrees C, whereas a dose of 2.5 micrograms/kg causes an increase in body temperature. Pretreatment with naloxone (4 mg/kg, 30 min before SP) suppresses the hypothermic effect. In spontaneously hypertensive rats (SHR), however, SP does not alter the body temperature. This result points to an altered thermoregulation in SHR based on changes in endorphin systems.
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PMID:[On the role of substance P in thermoregulation of normotensive and spontaneously hypertensive rats (author's transl)]. 617 84

The effects of substance P (SP), angiotensin II, oxotremorine and prostaglandin D2 (PG D2) on thyrotropin-releasing hormone (TRH) and thyrotropin (TSH) secretion in rats were studied. Either SP (100 micrograms/kg), angiotensin II (500 micrograms/kg), oxotremorine (1.0 mg/kg) or PGD2 (500 micrograms/kg) was injected intravenously or intraperitoneally, and the rats were serially decapitated. TRH, TSH and thyroid hormone were measured by means of a specific radioimmunoassay for each. The hypothalamic immunoreactive TRH (ir-TRH) contents were significantly increased by oxotremorine or SP and significantly decreased by angiotensin II, but no by PG D2. The plasma ir-TRH concentrations were significantly increased by angiotensin II, but not by oxotremorine, SP or PG D2. The plasma TSH levels were significantly increased by angiotensin II and significantly decreased by oxotremorine, SP or PG D2 in a dose-related manner. The plasma ir-TRH and TSH responses to cold were inhibited by oxotremorine, SP or PG D2, but enhanced by angiotensin II. The plasma TSH response to TRH was inhibited by SP, but enhanced by angiotensin II. The plasma TSH response to TRH did not differ from that of the control after PG D2 injection. In the haloperidol- or para-chlorophenylalanine (PCPA)-pretreated group, the inhibitory effect of PG D2 or oxotremorine on TSH release was prevented, while in the L-DOPA- or 5-hydroxytryptophan (5-HTP)-pretreated group, the inhibitory effect of SP on TSH release was prevented.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of substance P, angiotensin II, oxotremorine and prostaglandin D2 on thyrotropin secretion in rats. 620 27

Substance P (SP) and its COOH-terminal fragment (6-11) were coupled to bovine serum albumin by glutaraldehyde and used to elicit antibodies. Anti-SP and anti-SP6-11 antibodies bound to the same extent 125I-[Tyr8]-SP and 125I-[T-Lys6]-SP6-11. The latter was obtained after conjugation of the [Lys6]-SP6-11 with cold Bolton-Hunter reagent and then labelling by the chloramine-T method. In contrast to 125I-[Tyr8]-SP, 125I-[Tyr8]-SP6-11 was poorly bound by both anti-SP and anti-SP6-11 antibodies. Synthetic fragments of SP shorter than SP7-11 did not react with anti-SP6-11 antibodies. It is concluded that the antigenic determinant is within the COOH-terminal pentapeptide, and that Phe7, Phe8, Leu10 and Met11 contribute significantly to both anti-SP and anti-SP6-11 immunoreactivity.
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PMID:Immunogenic and antigenic properties of the COOH-terminal hexapeptide of substance P. 620 58

Neurotensin (NT) and bombesin, which are heterogeneously distributed in both brain and gastrointestinal tissue of several mammalian species, inhibit the formation of stress-induced gastric ulcers in rats. Many other endogeneous neuropeptides have also been reported to be present in brain and gastrointestinal tissue. The present study was conducted to evaluate the effect of some of these peptides on the development of cold-restraint stress (CRS)-induced gastric ulcers in rats. In addition, the effect of thyrotropin-releasing hormone (TRH), which antagonizes many of the CNS effects of NT, was investigated to determine whether this tripeptide antagonizes the cytoprotective effect of NT in this CRS model. All peptides were initially administered intracisternally (ic) in doses equimolar to 30 micrograms NT. As previously reported, NT (30 micrograms, ic) completely prevented the development of gastric ulcers in rats exposed to three hours of CRS. Bombesin, beta-endorphin, substance P, and somatostatin also exhibited cytoprotective activity. Several other peptides studied in the CRS model exerted no significant effects on the development of gastric ulcers; these included cholecystokinin octapeptide, gastrin, leu-enkephalin, met-enkephalin, and bradykinin. Two peptides, vasoactive intestinal polypeptide and TRH, significantly increased the severity of gastric ulcerations. The cytoprotective effect of NT was dose dependent. In contrast, lower doses of beta-endorphin, substance P, and somatostatin were cytoprotective whereas higher doses were not. Finally, concomitant ic injections of TRH antagonized the cytoprotective effects of NT and bombesin, but not that of beta-endorphin. The present results suggest that certain brain peptides may participate in modulating the gastric mucosal barrier, thereby increasing or decreasing its vulnerability to stress-induced lesions.
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PMID:The effect of centrally administered neuropeptides on the development of stress-induced gastric ulcers in rats. 630 95

To determine the role of NK-1 substance P receptors and N-methyl-D-aspartate (NMDA) and non-NMDA glutamate receptors in the spinal dorsal horn in the hyperalgesia induced by repeated cold stress (RCS), we examined the effects of intrathecal injections of antagonists to NK-1, NMDA and non-NMDA receptors on the nociceptive threshold of RCS rats for paw-pressure stimulation. Intrathecal injections of the NK-1 antagonist (2S,3S)-cis-2-(diphenylmethyl)-N-[(2-methoxyphenyl)-methyl]-1- azabicyclo[2.2.2]octan-3-amine (CP-96,345, 0.3-3 nmol/rat), the NMDA antagonist 2-amino-5-phosphonovaleric acid (APV, 1-10nmol/rat), and the non-NMDA antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 1-10 nmol/rat) suppressed RCS-induced hyperalgesia in a dose-dependent manner, without affecting the nociceptive threshold of normal rats. Combinations of any two of CP-96,345 (3 nmol/rat), APV (10 nmol/rat), and CNQX (10 nmol/rat) did not produce a larger inhibition than that produced by their single doses. The present results suggest that the enhancement of the substance P-NK-1 receptor system and glutamate-NMDA and non-NMDA receptor systems in the spinal dorsal horn is at least partly involved in the RCS-induced hyperalgesia.
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PMID:Effects of intrathecally injected glutamate and substance P antagonists on repeated cold stress-induced hyperalgesia in rats. 753 76


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