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)

Triple-labelling immunofluorescence and retrograde axonal tracing with fluorescent dyes have been combined to identify and characterize the neuropeptide content of vasoconstrictor, vasodilator and pilomotor neurons in the lumbar sympathetic ganglia of guinea-pigs. Postganglionic noradrenergic pilomotor neurons lacked immunoreactivity to neuropeptide Y and comprised up to about 30% of postganglionic neurons. Most post-ganglionic noradrenergic neurons that contained neuropeptide Y immunoreactivity were likely to be vasoconstrictor neurons, although some noradrenergic neurons containing neuropeptide Y projected to pelvic viscera. Vasoconstrictor neurons comprised up to about 60% of postganglionic neurons. About 15% of postganglionic neurons were non-noradrenergic and contained immunoreactivity to vasoactive intestinal peptide, neuropeptide Y and dynorphin. They mostly innervated blood vessels supplying skeletal muscles and were likely to be vasodilator neurons. Endings of presumed preganglionic neurons containing immunoreactivity to substance P were exclusively associated with vasodilator neurons. Conversely, presumed preganglionic endings containing immunoreactivity to calcitonin gene-related peptide were exclusively associated with vasoconstrictor neurons, although not all vasoconstrictor neurons had such endings associated with them. Presumed preganglionic terminals containing immunoreactivity to enkephalin were associated with some postganglionic neurons in each functional class. These results show that preganglionic and postganglionic sympathetic neurons lying in different functional pathways can be distinguished by their neuropeptide content as well as their projections. The identification of neurochemically distinct functional pathways begins to explain how the sympathetic nervous system is organized to allow the precise control of discrete target tissues.
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PMID:Vasoconstrictor, vasodilator and pilomotor pathways in sympathetic ganglia of guinea-pigs. 137 57

Repeated exposure of the rat vas deferens to the imidazoline oxymetazoline (OXY) results in a progressive loss of response which can appear selective for imidazoline agonists. The present study tests the hypothesis that imidazolines produce desensitization through prolonged blockade or inactivation of alpha-1 adrenoreceptors. Repeated exposure to OXY, naphazoline (NPZ) or tetrahydrozoline (THZ) produces a concentration- and time-dependent rightward shift and depression of the (-)-epinephrine concentration-effect curve, suggesting a mechanism of prolonged receptor blockade or inactivation. (-)-Epinephrine Kd values were similar when estimated after either receptor inactivation with phenoxybenzamine or repeated exposure to imidazolines. The differences in the ability of individual imidazolines to produce desensitization (order of potency: OXY greater than NPZ greater than or equal to THZ) do not follow their intrinsic activity (NPZ approximately THZ approximately OXY) or affinity (OXY greater than or equal to NPZ greater than THZ). The ability of individual imidazoline and phenethylamine agonists to produce a response in imidazoline-desensitized rat vas deferens reflects agonist intrinsic efficacy. Desensitization by imidazoline exposure does not affect contraction produced by either KCl or neurokinin A. Imidazolines produce effects similar to receptor inactivation and their desensitization in vas deferens can be explained without invoking an imidazoline subtype of alpha-1 adrenoreceptor.
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PMID:Imidazoline desensitization of epinephrine responses in rat vas deferens. 168 17

Adrenal and nonadrenal sympathetic preganglionic neurones (SPNs) in the intermediolateral nucleus of spinal segments T8-T10 in the cat were compared according to their responses to iontophoretic application of serotonin, substance P, and thyrotropin-releasing hormone (TRH). Responses of both types of SPN to iontophoretic application of serotonin were characterized by an increase in the rate of discharge that was slow in onset (mean +/- SD = 36 +/- 21 s) and prolonged in afterdischarge (115 +/- 70 s) following termination of application. Depression was never observed and responses were similar whether using serotonin at a pH of 3.3 or 4.5, suggesting that the absence of a depressant effect cannot be accounted for by pH, as has been reported with cortical neurones. Iontophoretic application of methysergide resulted in a decrease in the rate of discharge of both types of SPN and blocked the excitatory responses to serotonin. Adrenal and nonadrenal SPNs were excited by iontophoretic application of substance P. Responses of both types of SPN were similar and were characterized by a gradual increase in the rate of discharge that was slow in onset (42 +/- 27 s) and prolonged in afterdischarge (96 +/- 42 s). Finally, adrenal and nonadrenal SPNs were also weakly excited by iontophoretic application of TRH. These responses were slow in onset (48 +/- 27 s) and prolonged in afterdischarge (78 +/- 35 s). These data indicate that serotonin, substance P, and TRH exert excitatory effects on functionally dissimilar sympathetic preganglionic neurones and support the possibility that they may be chemical mediators of synaptic transmission in the intermediolateral nucleus. In addition, these data may be interpreted to support the notion that serotonin, substance P, and TRH are involved in global activation of the sympathetic nervous system.
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PMID:Adrenal versus nonadrenal sympathetic preganglionic neurones in the lower thoracic intermediolateral nucleus of the cat: effects of serotonin, substance P, and thyrotropin-releasing hormone. 169 19

Intralobular (granular) salivary ducts were purified by isopycnic centrifugation after collagenase/hyaluronidase digestion of the rat submandibular gland. The resulting ductal fraction (density, 1.056 +/- 0.003) was highly enriched in kallikrein (a ductal cell marker) and contained little amylase activity (an acinar cell marker). The resting intracellular calcium level in the ductal preparation was 103 +/- 4 nM. Increased intracellular calcium concentrations (2-3 times resting levels) were observed in response to muscarinic (carbachol) and alpha-adrenergic (epinephrine) agonists, but little response was observed to substance P, suggesting the absence of substance P peptidergic receptors on rat submandibular ducts. Intracellular adenosine 3',5'-cyclic monophosphate levels were increased 35-fold in response to beta-adrenergic stimulation (isoproterenol) and forskolin. The ducts secreted kallikrein in response to epinephrine, carbachol, and isoproterenol but not in response to substance P. Epinephrine was the most potent inducer of kallikrein release with a K0.5 of approximately 3 microM and a maximal secretory rate approximately nine times unstimulated levels. Taken together, these results provide strong evidence for the functional integrity of the ductal preparation. This preparation should prove useful for the further elucidation of the properties of intralobular salivary ducts structures which heretofore have only been studied indirectly.
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PMID:Isolation and characterization of rat submandibular intralobular ducts. 171 52

Neuropeptides, including substance P (SP), calcitonin gene-related peptide (CGRP) and somatostatin (SS) in dorsal root ganglia (DRG) may play a role in neurogenic inflammation and pain transmission. Adrenal corticosteroids regulate neuropeptide synthesis in some areas of the CNS and may modulate neurogenic inflammation and sensory perception. We have investigated the effects of adrenalectomy and dexamethasone (0.2 mg/kg/day) treatment on neuropeptide content of rat cervical DRG using specific and sensitive radioimmunoassays. In control animals, a differential distribution of neuropeptide was found; SP and CGRP content increased from C4 to C7 in contrast to SS content, which decreased from C4 to C7. Ten days following adrenalectomy, the mean SS content of cervical DRG decreased significantly to 79.6 +/- 4.5% of sham-operated controls. In contrast, SP and CGRP content increased significantly 10 days after adrenalectomy to 134.6 +/- 6.9% and 132.0 +/- 11.6% of sham-operated controls, respectively. The effects of adrenalectomy on CGRP and SS were reversed by administration of dexamethasone. These results suggest that glucocorticoids affect the neuropeptide content of DRG in the adult rat.
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PMID:Effect of adrenalectomy and dexamethasone on neuropeptide content of dorsal root ganglia in the rat. 172 40

Adrenal medullary tissue was collected from parkinsonian patients at autopsy and at the time of autologous transplantation of the adrenal medulla to the caudate nucleus, and from nonparkinsonian patients at autopsy and during nephrectomy. Levels of the following neuropeptides were measured by radioimmunoassay in samples of the medullary tissue: neuropeptide Y (NPY), substance P (SP), [Met]enkephalin ([Met]ENK), vasoactive intestinal peptide (VIP), peptide YY, and bombesin-like immunoreactivity. Regression analysis was used to establish a relationship between patient age, time to organ harvest, and peptide levels in nonparkinsonian tissue. Levels of [Met]ENK, VIP, NPY, and SP were significantly lower in parkinsonian adrenal medullae than that predicted from the control group. These results suggest that the adrenal medulla of a parkinsonian patient is severely compromised, either by the disease process itself or by the antiparkinsonian medications used to treat the symptoms of the disease.
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PMID:Decreased levels of [Met]enkephalin, neuropeptide Y, substance P, and vasoactive intestinal peptide in parkinsonian adrenal medulla. 191 31

The last decade has seen tremendous progress in determining the nature of the neurotransmitters which regulate central nervous system pathways involved in the regulation of blood pressure. Investigations are now pursuing the identity and functional importance of neurotransmitters contained within pathways shown to be important in cardiovascular regulation. In addition, several key components of the brain stem networks involved in the control of sympathetic activity have been identified. For example, numerous studies indicate the importance of neurons located in the rostral ventrolateral medulla in the regulation of SPN. Indeed, this area contains medullospinal sympathoexcitatory neurons which represent the final site of integration of many brain stem and reflex pathways involved in the regulation of sympathetic nerve activity. The neurotransmitter which is utilized by this medullospinal pathway remains unknown. Epinephrine, substance P and glutamate have all been hypothesized as primary chemical mediators in the descending pathway from the brain stem to SPN. Interestingly, lesions of, or antagonists to, epinephrine, substance P, glutamate and 5-HT neurons all abolish sympathetic activity and reduce blood pressure to a level similar to that in a spinal animal. Clearly, not all these transmitters are primary mediators of sympathetic information carried from the brain stem to the spinal cord. It is likely that monoamines and neuropeptides act in the IML, as in other area of the central nervous system, as neuromodulators to set the level of excitability of SPN rather than relaying sympathetic information over a functionally specific medullospinal pathway. This conclusion is supported by the observation that midline medullary 5-HT neurons provide a tonic excitatory input to SPN, but receive no afferent inputs from other central sympathetic or baroreceptor pathways. However, the firing of 5-HT neurons appears to relate to the state of vigilance of the animal. This suggests that 5-HT neurons may lower the threshold of SPN to sympathetic inputs during states of wakefulness. In addition, the time course of the norepinephrine-mediated slow EPSPs and IPSPs in SPN is consistent with a gain-setting function. By analogy, epinephrine is likely to act as a neuromodulator in the IML rather than to serve as the primary mediator of sympathetic information descending from the rostral ventrolateral medulla.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Role of neurotransmitters in the central regulation of the cardiovascular system. 198 Dec 83

Administration of 10 micrograms of substance P intrathecally to the spinal T9 level of the adult rat, anaesthetized with urethane, provoked an increase in free catecholamines in plasma taken from the inferior vena cava. Adrenaline levels at 1 min after administration were 154.8 +/- 10.8% (mean +/- SE; n = 11) of preadministration levels and noradrenaline levels were 153.5 +/- 11.8% of preadministration levels. Differences between the values of free catecholamines in animals given substance P vs those given vehicle only were statistically significant at 1 and 10 min postinjection, but not at 30 min. Administration of a substance P analogue with central antagonistic properties 15 min before substance P was given prevented expression of the effects of substance P. These results suggest that substance P may be an excitatory chemical mediator of synaptic transmission in spinal pathways controlling adrenal medullary output. Thus dysfunction of substance P mechanisms may underlie some animal models of hypertension and may be involved in some cases of essential hypertension in man as well as in autonomic dysfunction associated with some neurological entities.
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PMID:Substance P given intrathecally at the spinal T9 level increases adrenal output of adrenaline and noradrenaline in the rat. 241 Aug 14

We have studied the involvement of sensory nerves containing substance P (SP) in the modulation of stress-induced catecholamine (CA) secretion from the sympathetic nervous system and adrenal medulla. Adrenaline and noradrenaline (NA) levels were measured in blood samples withdrawn from the inferior vena cava (i.v.c.) at 5 or 15 min intervals for periods of up to 60 min, in adult rats during stress induced by insulin or cold. Insulin stress caused a biphasic elevation of plasma CA. Previous studies from our laboratory have shown that the first phase lasting 30 min is neurogenic, and the second phase from 30 to 60 min is non-neurogenic in mechanism. In control adult rats (with normal levels of SP in their splanchnic nerve), insulin stress caused a slow and progressive secretion of adrenaline into the circulation for the first 30 min (neurogenic phase). In the period 30-60 min (non-neurogenic phase) plasma adrenaline and NA levels rose at a much higher rate. In capsaicin-pre-treated rats (in which SP levels in the splanchnic nerve were depleted by 68%) insulin stress produced a steady increase in plasma adrenaline levels for up to 5 min similar to that in insulin-stressed control animals; however, by 10 min the plasma adrenaline levels had fallen to basal and remained low up to 30 min. From 30 to 60 min, plasma adrenaline and NA levels rose steeply as seen with control animals. We conclude that capsaicin pre-treatment affected the neurogenic phase but did not affect the non-neurogenic phase. Cold stress increased the plasma adrenaline levels by a neurogenic mechanism over 30 min in control rats. In contrast, in capsaicin-pre-treated, cold-stressed rats, plasma adrenaline did not increase significantly. Plasma NA levels were also significantly lowered in capsaicin-pre-treated, cold-stressed rats during the neurogenic phase but NA increases were not dependent on an intact adrenal innervation. The results using both insulin stress and cold stress suggest that capsaicin-sensitive (sensory) nerve fibres in the adrenal medulla and in sympathetic ganglia are capable of modifying the secretory responses of these tissues to stress. Results from our previous in vitro work are compatible with the view that SP may be the neuromodulator released from such sensory nerves to produce these effects. This suggests that the previously reported ability of SP to modulate nicotinic receptor function in vitro by either inhibiting the nicotinic response or protecting against nicotinic desensitization may be more than a mere pharmacological curiosity.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:The role of sensory fibres in the rat splanchnic nerve in the regulation of adrenal medullary secretion during stress. 242 Sep 73

The effects of intrathecally administered arginine-vasopressin (AVP) and substance P (SP) on adrenal medullary secretion of epinephrine were examined in anesthetized Sprague-Dawley rats. Plasma epinephrine levels were measured in blood samples taken directly from the adrenal vein using a novel micropuncture technique. The blood samples (20-30 microliter in volume) were taken before, and 2 min, 15 min and 30 min after intrathecal injections of AVP, SP or vehicle only. Plasma was assayed for epinephrine using high pressure liquid chromatography. Adrenal venous epinephrine levels were not significantly altered by the intrathecal administration of AVP, thereby suggesting that adrenal epinephrine secretion is not involved in the cardiovascular responses previously reported to occur following similar doses of intrathecal AVP. Intrathecal SP administration, while causing blood pressure responses similar to those produced by AVP, resulted in significant increases in adrenal vein epinephrine. This finding suggests that activation of adrenal secretion of epinephrine may contribute to SP-initiated blood pressure changes.
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PMID:The effects of intrathecal administration of arginine-vasopressin and substance P on blood pressure and adrenal secretion of epinephrine in rats. 242 66


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