UNIPROT:P20366 - FACTA Search

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Query: UNIPROT:P20366 (substance P)
21,176 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. In guinea-pig isolated bronchus treated with indomethacin (2.8 microM), electrical field stimulation (EFS; 10 Hz, 0.5 ms, 60-70 V, for 10 s) evoked a tetrodotoxin (3 microM)-sensitive, biphasic contraction comprising a rapid, atropine (1 microM)-sensitive cholinergic response succeeded by a slowly developing, capsaicin (10 microM)-sensitive, non-adrenergic, non-cholinergic excitatory (NANCe) response. 2. BRL 38227 (0.3-3 microM), salmeterol (0.003-3 microM) and ketotifen (1.0-300 microM) each produced concentration-dependent inhibition of both NANCe and cholinergic responses to EFS in guinea-pig isolated bronchus. 3. Substance P (SP; 1 microM) and neurokinin A (NKA; 0.07 microM) produced contractions equivalent in magnitude to the NANCe response to EFS, which were inhibited by salmeterol (1 microM), but not by BRL 38227 (3 microM) or ketotifen (100 microM). 4. Acetylcholine (ACh; 6 microM) was equi-effective with the electrical activation of cholinergic neurones. BRL 38227 (3 microM) slightly inhibited responses to ACh (6 microM). Salmeterol (1 microM) and ketotifen (100 microM) markedly inhibited responses to ACh (6 microM). 5. In bronchial rings pre-contracted with ACh (100 microM), BRL 38227 (0.1-30 microM), salmeterol (0.001-3 microM) and ketotifen (0.1-100 microM) each produced concentration-dependent relaxation. Unlike ketotifen, BRL 38227 and salmeterol only partially (18.8 +/- 2.1% and 51.8 +/- 3.9% respectively) reversed the ACh-induced contraction. 6. The (+)-analogue of BRL 38227, BRL 38226 (0.3-100 microM), was without effect on responses to EFS and had no effect on the inhibition caused by BRL 38227. The K+-channel activators pinacidil (3.0-30 microM) and RP 52891 (3.0-30 microM) exerted similar inhibitory actions on responses to EFS as BRL 38227, but were less potent. Glibenclamide (0.1-1.O microM) and phentolamine (3 microM) antagonized the inhibitory effects of BRL 38227 on responses to EFS.7. It is concluded that BRL 38227 and ketotifen can inhibit NANCe neuroeffector transmission at concentrations exerting little or no inhibitory effects on responses to exogenously applied tachykinins.By contrast, in addition to suppressing NANCe responses to EFS, salmeterol also markedly inhibits responses to SP and NKA. At concentrations markedly suppressing cholinergic neuroeffector transmission, BRL 38227 has only minor effects on responses to exogenously-applied ACh. Salmeterol and ketotifen both depress responses to ACh within the concentration-range over which they inhibit cholinergic responses to EFS. The inhibitory effects of BRL 38227 on responses to EFS exhibit stereo-specificity and may involve the opening of a neuronal K+-channel. This K+-channel is glibenclamide-and phentolamine-sensitive and appears similar to the smooth muscle K+-channel which is modulated by BRL 38227.
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PMID:Effects of BRL 38227 on neurally-mediated responses in the guinea-pig isolated bronchus. 150 20

We investigated the influence of exogenously administered acetylcholine, nitric oxide, ADP, ATP, bradykinin, and substance P on coronary vascular tone in isolated, neonatal pig hearts (less than or equal to 4 d). Paced (180 bpm), isovolumically beating hearts underwent retrograde aortic perfusion, with an erythrocyte-enriched solution (hematocrit 0.15-0.20) at constant coronary flow (approximately 2.5 mL/min/g) corresponding to a perfusion pressure of approximately 60 mm Hg. Agonists were injected into the aortic root, and the peak change in coronary perfusion pressure from baseline and left ventricular pressure development were assessed. Nitric oxide (3 microL), ADP (30 nmol), ATP (30 nmol), bradykinin (125 ng), and substance P (50 ng) decreased the perfusion pressure (vasodilation) by 16.9 +/- 1.2, 25.3 +/- 4.4, 18.3 +/- 1.2, 18.9 +/- 1.4, and 7.1 +/- 1.6 mm Hg, respectively. Acetylcholine (0.5 and 1.0 nmol) produced a modest decrease in perfusion pressure (vasodilatation) of 4.2 +/- 0.8 and 3.8 +/- 0.5 mm Hg, respectively, whereas acetylcholine (5, 20, and 100 nmol) increased the perfusion pressure (vasoconstriction) by 16.7 +/- 2.7, 48.2 +/- 8.2, and 85.3 +/- 15.1 mm Hg, respectively. Acetylcholine also decreased left ventricular peak systolic pressure from 108.7 +/- 5.0 to 69.2 +/- 4.6, 56.3 +/- 6.1, and 48.2 +/- 6.4 mm Hg, for the 5, 20, and 100 nmol doses, respectively. Responses to acetylcholine were abolished by atropine (50 nmol). In a separate group of hearts, indomethacin (10(-6) M) reduced the peak change in perfusion pressure for the 5, 20, and 100 nmol doses of acetylcholine by 87%, 66%, and 48%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Acetylcholine-induced coronary vasoconstriction and negative inotropy in the neonatal pig heart. 150 17

The ability of Acetylcholine (ACh) and A23187 to induce endothelium-dependent relaxation was compared in the isolated perfused mesenteric arterial bed of untreated adult rats, adult rats treated neonatally with capsaicin, and adult rats treated as adults with capsaicin. Following neonatal capsaicin treatment, the response to both agents was reduced. Following adult treatment, the response to both agents was reduced seven days following capsaicin treatment. The same results were obtained in the presence of L-arginine or indomethacin. Tissues from all rats responded equally to sodium nitroprusside. Following capsaicin treatment no change in the structural relationship of the arterial intima was detected but no perivascular nerve fibres immunoreactive to substance P (SP) or calcitonin gene-related peptide (CGRP) could be demonstrated. It is suggested that the reduced response to ACh and A23187 does not involve a change in endothelial muscarinic receptors or a structural change in the arterial intima, but is directly related to the absence of immunohistochemically demonstrable CGRP/SP-containing perivascular innervation.
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PMID:Peptidergic nerve involvement in the control of endothelium-dependent vascular relaxation. 152 74

Neurons expressing the m1, m2, and m4 muscarinic receptor genes in the adult rat striatum were identified and characterized by using several in situ hybridization and immunohistochemical procedures. Combined in situ hybridization for the simultaneous detection of two mRNAs in the same section or in adjacent sections as well as in situ hybridization and immunohistochemistry on adjacent sections permitted us to identify the neurons containing m1, m2, or m4 receptor mRNA. Our observations demonstrate that m1, m2, and m4 receptor genes are expressed in one or several phenotypically distinct neuronal populations. The m1 receptor gene was the most widely expressed (85% of the striatal neurons). Most cholinergic neurons (80% or more) contain m1, m2, and m4 receptor mRNAs. Almost all the substance P neurons contain m1 and m4 receptor mRNA. All enkephalinergic neurons contained m1 receptor mRNA, but only 39% contained m4 receptor mRNA. Most somatostatin and neurotensin neurons expressed the m1 receptor gene, but only a few (15% and 9%, respectively) contained m4 receptor mRNA. The present study offers anatomical evidence that ACh may act directly in complex ways on the main neuronal populations of the striatum through muscarinic receptors. The m1, m2, and m4 receptors may act as autoreceptors to control ACh release and possibly other parameters of ACh neurons. On the other hand, the m1 and m4 receptors may act as heteroreceptors in cholinoceptive efferent neurons (enkephalin and substance P neurons) and other neurons (somatostatin/neuropeptide Y and neurotensin neurons). The presence of m4 receptor mRNA in only parts of the enkephalin, somatostatin, and neurotensin neuronal populations indicates that muscarinic receptor gene expression contributes to the functional and anatomical heterogeneity of the striatum that may relate to higher order of organization, including patch-matrix compartmentalization. The wide expression of m1 and m4 receptor genes in the striatum suggests that ACh may directly influence neurotransmitter release and synthesis in striatal efferent and intrinsic neurons. Our results imply that the specific pattern of expression of the muscarinic receptor genes mediates direct effects of ACh on activities and functions of chemically and topologically defined striatal neuronal populations. Since the expression of muscarinic receptors occurred in the three main neuronal populations of the striatum, namely ACh, enkephalins, and substance P neurons that also express dopamine receptors, it is highly probable that ACh and dopamine may act together at the single-cell level to influence striatal functions.
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PMID:Phenotypical characterization of the rat striatal neurons expressing muscarinic receptor genes. 152 98

Myenteric plexus neurons derived from neonatal guinea pigs, when exposed to serum, demonstrated a characteristic pattern of growth, including a proliferating outgrowth zone of glial cells, peripheral extension of dendritic processes, and progressive dendritic growth. Serum effects upon dendritic growth, measured morphometrically, was strongly dose- and temporally dependent. Dendritic density was increased 10-fold (120 hr) by the addition of 6% serum, while mean dendritic length was increased 3-fold. Development of cholinergic function was reflected by release of [3H]ACh in response to cholecystokinin octapeptide, vasoactive intestinal peptide, substance P, and calcitonin gene-related peptide (10(-10) and 10(-8) M).
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PMID:Dendritic outgrowth of myenteric plexus neurons in primary culture. 159 70

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)
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PMID:Neurokinin receptors differentially mediate endogenous acetylcholine release evoked by tachykinins in the neostriatum. 165 75

An important component of neuronal development is the matching of neurotransmitter expression with the appropriate target cell. We have examined how peptide transmitter expression is controlled in a simple model system, the avian ciliary ganglion (CG). This parasympathetic ganglion contains 2 distinct types of neurons: choroid neurons, which project to vasculature in the eye's choroid layer and use somatostatin as a co-transmitter with ACh, and ciliary neurons, which innervate the ciliary body and iris and use ACh but no known peptide co-transmitter. We have found that the earliest developmental stage in which neurons with somatostatinlike immunoreactivity (SOM-IR) are consistently found in vivo is stage 30 (embryonic day 6.5), a time shortly after the extension of neurites to targets in the eye's choroid layer. In cell culture, CG neurons expressed SOM-IR in co-culture with choroid cells, but not when cultured with striated muscle myotubes or with ganglion non-neuronal cells. No significant differences in neuronal survival or in ChAT activity were observed under these different co-culture conditions, which suggests that somatostatin expression is independently regulated. The stimulation of somatostatin expression was also specific in that other neuropeptides commonly found in autonomic neurons [neuropeptide Y (NPY), substance P (SP), vasoactive intestinal polypeptide (VIP)] were not induced in the presence of choroid cells. The ability to stimulate SOM-IR was not contact dependent because a macromolecule of greater than or equal to 10 kDa in choroid-conditioned medium (ChCM) was found to stimulate somatostatin expression in a dosage-dependent fashion. The somatostatin-stimulating activity induced SOM-IR in more than 90% of CG neurons, as well as in retrogradely labeled ciliary neurons, which would not normally express SOM-IR. Thus, the expression of somatostatin in cultured CG neurons is regulated by a macromolecule produced by cells in the choroid layer, a target normally innervated in vivo by CG neurons expressing somatostatin.
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PMID:Stimulation of somatostatin expression in developing ciliary ganglion neurons by cells of the choroid layer. 167 9

Negative chronotropic and vasodilator responses of the isolated perfused guinea pig heart to substance P (SP) were evaluated. Bolus injections of 2.5, 25 and 125 nmol of SP caused a dose-dependent bradycardia, with the largest dose decreasing heart rate by 53% of base line. Pretreatment with 1 microM atropine blocked the negative chronotropic response to 25 nmol of SP. Pretreatment with 0.5 microM neostigmine lowered base-line heart rate and potentiated the negative chronotropic response to 25 nmol of SP. A potent vasodilator response to SP was demonstrated after elevation of base-line perfusion pressure with 1 microM [Arg8]vasopressin or 40 mM KCl. The vasodilator effect of SP was dose-dependent and occurred at much lower doses than required to affect heart rate. The ED50 for vasodilation was less than 1 pmol in both preparations. In hearts with vascular tone increased by vasopressin, atropine (1 microM) decreased the maximum vasodilator response to SP by 23%, but neither atropine nor a combination of 10 microM cimetidine and 1 microM chlorpheniramine affected the ED50 for SP. These results suggest that SP causes bradycardia by stimulating cholinergic neurons and coronary vasodilation by some mechanism not involving either acetylcholine or histamine. Acetylcholine may, however, contribute to the maximum vasodilator response to SP.
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PMID:Effects of substance P on rate and perfusion pressure in the isolated guinea pig heart. 168 42

Neurokinins regulate gastrointestinal motility by interacting with receptors on both muscle layers and on myenteric plexus neurons. To determine if specific neurokinin (NK) receptor agonists can mediate inhibitory effects on myenteric neurons, we studied the effect of the NK-1 agonist substance P methylester (SPME) and the putative endogenous NK-2 receptor ligand neurokinin A (NKA) on [3H]acetylcholine [( 3H]ACh) release induced by electrical field stimulation from muscle strips cut from the canine gastric antrum. SPME but not NKA caused a dose-dependent inhibition of stimulated [3H]ACh release in tissues containing the myenteric plexus. The inhibition was not seen in longitudinal muscle without myenteric plexus. Pretreatment of tissues with indomethacin or antiserum to vasoactive intestinal polypeptide (VIP) but not naloxone or adrenergic or cholingergic blockade abolished the SPME-induced inhibition. Exogenous VIP stimulated the release of prostaglandin E2 (PGE2) from full thickness strips, and both VIP and PGE2 inhibited [3H]ACh release induced by electrical depolarization. These findings suggest that NK-1 receptor agonists can selectively inhibit stimulated [3H]ACh release and that this inhibition may involve the release of VIP and PGE2 from neurons within the myenteric plexus.
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PMID:Neurokinin inhibition of cholinergic myenteric neurons in canine antrum. 168 19

The nature of ATP release from mainly smooth muscles of guinea-pig was evaluated with KCl and agonists for different kinds of receptors. In ileal longitudinal muscles, amounts of net ATP release by ACh and bethanechol (1-10 microM) were much larger (about 10 fold) than that by other drugs, e.g., histamine, 5-hydroxytryptamine, prostaglandin-F2 alpha, substance P and bradykinin, including KC1, although differences between contractions of the tissue evoked by test drugs were approximately 1.5 times at most. The ATP release, as well as the contraction, evoked by ACh or bethanechol was markedly reduced by atropine (0.3 microM), thus, indicating primarily postjunctional release of ATP. The remarkable ATP release from vas deferens by norepinephrine (NE), but not by substance P, was abolished almost completely by prazosin (0.3 microM). Increases in intracellular Ca2+ and subsequent contraction in the ileal tissue were produced by ATP and these responses were fully antagonized by nifedipine (0.1 microM). These findings provide evidence that the drugs-stimulated ATP release from smooth muscles does not result from contractility of muscles, but is substantially elicited only by stimulation of neurotransmitter (NE or ACh) receptors, suggesting the existence of the receptor-stimulus-postjunctional ATP release coupling. The released ATP may contribute, in part, to the muscle contractility via increase of Ca2(+)-influx, presumably, in a manner related to the voltage-gated Ca2(+)-channels.
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PMID:A possible coupling of postjunctional ATP release and transmitters' receptor stimulation in smooth muscles. 169 69

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