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)

1. The tachykinin antagonist (D-Arg1, D-Cl2Phe5, Asn6, D-Trp7.9, Nle11)-substance P, injected intravenously, blocked salivary secretion from the ferret parotid and submandibular glands in response to subsequent i.v. injections of the tachykinins, substance P and neurokinin A. 2. The tachykinin antagonist reduced the parasympathetic nerve-evoked secretion of parotid and submandibular saliva by 15-20% and 35-40%, respectively. Atropine abolished the remaining secretory response. 3. The 'atropine-resistant' parasympathetic nerve-evoked secretion of saliva from the parotid and submandibular glands (about 5 and 30%, respectively, of that before administration of atropine) was abolished by the tachykinin antagonist. 4. The tachykinin antagonist was without effect on the protein concentration of parotid and submandibular saliva secreted in response to parasympathetic nerve stimulation. Parotid and submandibular saliva lacked amylase. 5. Atropine reduced the protein concentration of the submandibular saliva secreted in response to parasympathetic nerve stimulation by 50%; this was the protein concentration of substance P-evoked saliva. 6. The secretory response to methacholine and to stimulation of preganglionic sympathetic nerve fibres, tested in rats, was unaffected by the tachykinin antagonist, contra-indicating an unspecific action of the antagonist. 7. The results suggest that the neuronal release of tachykinins is probably important in the nerve-evoked secretory response of the parotid and submandibular glands.
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PMID:Tachykinin involvement in parasympathetic nerve-evoked salivation of the ferret. 246 Jan 78

Electrical field stimulation (EFS) was performed on rabbit proximal and distal circular colonic smooth muscle to study the mechanisms of neural control of the colon. Electrical pulses were applied with parallel silver plate electrodes to muscle that had been stretched to Lo. The proximal muscle demonstrated an on-contraction during EFS. In distal muscle, EFS initiated an on-relaxation, followed by an on-contraction and an off-contraction. The time delay for the on-contraction of distal muscle was longer by 2.5 +/- 0.5 s than was the delay in proximal muscle (p less than 0.02). The amplitudes of the on- and off-contraction were dependent on the frequency of the EFS. The on- and off-responses were completely inhibited by 3 x 10(-6) M tetrodotoxin. Atropine inhibited the distal on-contraction at all EFS frequencies and the proximal on-response at EFS frequencies less than 16 Hz. Atropine had a partial inhibitory effect on the distal off-response (approximately 30%). Bombesin and substance P were released during prolonged EFS. Desensitization of the distal colonic muscle to bombesin did not affect the distal off-contraction. However, desensitization of the tissue to substance P and exposure to substance P antagonists inhibited the distal off-contraction. These studies suggest that (a) acetylcholine mediates the on-contraction of the distal circular colonic muscle, and a major part of the on-contraction for the proximal muscle, and (b) substance P is responsible for the off-contraction of the distal muscle.
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PMID:Differences in the response of proximal and distal rabbit colonic muscle after electrical field stimulation. 246 3

We performed three consecutive dose-response curves to rapid intravenous infusions of substance P (SP) in anesthetized, mechanically ventilated guinea pigs. The dose of SP required to decrease pulmonary conductance to 50% of its base-line value (ED50GL) decreased 2.8-fold (P less than 0.002) and 3.3-fold (P less than 0.001) on the second and third dose-response curves, respectively, compared with the first. SP did not alter airway responses to intravenous histamine but did cause a significant (3.7-fold) decrease in ED50GL for dose-response curves to intravenous capsaicin, an agent that causes bronchoconstriction by release of endogenous tachykinins. The neutral metalloendopeptidase inhibitor thiorphan (0.5 mg) and the angiotensin-converting enzyme inhibitor captopril (1.7 mg) both caused a marked enhancement of airway responses to SP observed on the first dose-response curve but did not alter the enhancement of SP-induced airway responses produced by repeated SP challenge. The anticholinergic atropine (5 mg/kg iv), the antihistamine mepyramine (8 mg/kg iv), and the cyclooxygenase inhibitor indomethacin (30 mg/kg ip) had no effect on the first SP dose-response curve. Atropine and mepyramine did not prevent the enhancement of SP responses observed with repeated challenge, but after pretreatment with either indomethacin or acetylsalicylic acid, dose-response curves to SP were reproducible. Our results indicate that airway responses to intravenous SP are enhanced with repeated SP challenge and suggest that cyclooxygenase products of arachidonic acid metabolism are involved in the mediation of this phenomenon.
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PMID:Enhanced airway responses to substance P after repeated challenge in guinea pigs. 246 38

It has previously been found that, in the presence of naloxone, the ganglionic blocking drug hexamethonium fails to completely block peristaltic motility in the isolated ileum of the guinea-pig. This hexamethonium-resistant peristaltic activity is coordinated by enteric nerves since it is abolished by tetrodotoxin. In the present study the neurotransmitter circuitry of this type of peristalsis was studied by means of specific antagonists. Atropine totally suppressed hexamethonium-resistant peristalsis. This type of peristalsis was also strongly inhibited by the tachykinin antagonist, spantide, if a concentration sufficient to antagonize neuronally located substance P receptors was employed. In contrast, the cholecystokinin antagonist, lorglumide, caused only a slight inhibition of hexamethonium-resistant peristalsis. Both substance P and the cholecystokinin-related peptide, ceruletide, potently stimulated the hexamethonium-resistant type of peristaltic activity. These data indicate that, after blockade of nicotinic acetylcholine receptors, tachykinins mediate neuroneuronal coordination of peristalsis whereas acetylcholine acting via muscarinic receptors may be primarily responsible for neuromuscular transmission. Cholecystokinin-like peptides appear to play a modulator rather than a mediator role in hexamethonium-resistant peristalsis.
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PMID:Evidence for an involvement of substance P, but not cholecystokinin-like peptides, in hexamethonium-resistant intestinal peristalsis. 247 70

1. 'Atropine-resistant' secretion of saliva in response to parasympathetic stimulation may reflect antidromic activation of sensory nerve fibres. In this investigation, the effect of pretreatment in the rat with capsaicin (total dose of 125 mg kg-1, s.c.), was determined. 2. In the parotid glands substance P (SP)/calcitonin gene-related peptide (CGRP)-containing nerve fibres around ducts and blood vessels disappeared after capsaicin, while periacinar SP-containing fibres (devoid of CGRP) and CGRP-containing fibres (devoid of SP) remained. Vasoactive intestinal peptide (VIP)-containing nerve fibres seemed to be unaffected. The parotid content of SP and CGRP was reduced by 11 and 36% respectively, while that of VIP remained unchanged. 3. The weights of the parotid glands and their sensitivity to the secretagogues methacholine and SP, injected intravenously, were unchanged as was the response to stimulation of the auriculo-temporal nerve in the presence and absence of atropine. 4. In contrast to capsaicin pretreatment, parasympathetic denervation of the parotid gland reduced the weight of the gland and produced an increase in the response to methacholine and SP. 5. For comparison, the effectiveness of the capsaicin treatment on neuropeptide content was determined in the urinary bladder. The bladder of capsaicin-pretreated rats increased in weight (21%) and in VIP content (31%), while the content of SP and CGRP was reduced by 86 and 94%, respectively. SP- and CGRP-containing nerve fibres were virtually eliminated, while VIP-containing nerve fibres seemed unaffected. 6. In conclusion, antidromic activation of primary afferent (capsaicin-sensitive) C-fibres does not contribute significantly to the 'atropine-resistant' secretory response of the parotid gland to stimulation of the parasympathetic nerve.
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PMID:Effects of capsaicin pretreatment on neuropeptides and salivary secretion of rat parotid glands. 247 1

The components of the intestinal peristaltic reflex in humans were examined and the neurotransmitters responsible for them identified for the first time i isolated flat sheet segments of intestine. Increasing radial stretch to the caudad end elicited increasing ascending contraction only, whereas increasing radial stretch to the orad end elicited increasing descending relaxation only. Both components were abolished by hexamethonium, implying the participation of cholinergic interneurons in each component. Atropine inhibited ascending contraction only, abolishing the response to low grades of stretch and partially inhibiting the response to high grades of stretch (69% +/- 17%, p less than 0.01). The substance P antagonist [D-Pro2, D-Trp7,9] substance P partially inhibited ascending contraction induced by high grades of stretch only (40% +/- 12%, p less than 0.02). The vasoactive intestinal peptide antagonist [4-Cl-D-Phe6, Leu17]vasoactive intestinal peptide inhibited descending relaxation, abolishing the response to low grades of stretch and partially inhibiting the response to high grades of stretch (40% +/- 4%, p less than 0.001). Release of vasoactive intestinal peptide increased significantly by 91% during descending relaxation only, whereas release of both substance P and substance K increased significantly by 107% during ascending contraction only, supporting the participation of vasoactive intestinal peptide motor neurons in descending relaxation and tachykinin motor neurons as well as cholinergic motor neurons in ascending contraction. The components of the human peristaltic reflex and transmitters regulating them were identical to those found in rat and guinea pig intestine.
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PMID:Identification of neurotransmitters regulating intestinal peristaltic reflex in humans. 247 88

The role of tachykinin neurons of the myenteric plexus in the regulation of the intestinal peristaltic reflex was examined in rat colonic segments that enable separate measurement of ascending contraction and descending relaxation. Release of immunoreactive substance P (SP) and substance K (SK) increased (68% for SP; 70% for SK) during ascending contraction and decreased (37% for SP; 13% for SK) during descending relaxation. Exogenous SP and SK augmented ascending contraction and inhibited descending relaxation. Neither SP antiserum nor SK antiserum had any effect on descending relaxation. The antisera had no effect also on ascending contraction induced by low grades of stretch (2 g), but they inhibited significantly contraction induced by high grades (6-10 g) of stretch (52 +/- 8% inhibition with SP antiserum and 48 +/- 8% with SK antiserum). A combination of both antisera abolished ascending contraction induced by high grades of stretch. Atropine inhibited only partially ascending contraction at high grades of stretch. The pattern of inhibition by both antisera and by atropine implied that ascending contraction induced by high grades of stretch was mediated by tachykinin neurons acting directly on smooth muscle cells as well as indirectly via release of acetylcholine from cholinergic motor neurons.
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PMID:Tachykinins as transmitters of ascending contractile component of the peristaltic reflex. 248 Jul 18

We have investigated whether the histamine H3-receptors influence nonadrenergic noncholinergic (NANC) bronchoconstriction in guinea-pig in vivo. Atropine, propranolol, mepyramine and cimetidine were administered to block the effects of beta-adrenoceptor-, acetylcholine, H1- and H2-receptor-mediated responses, respectively. Vagal stimulation evoked a NANC bronchoconstrictor response. The selective H3-agonist, alpha-methylhistamine (alpha-MeHA, 1-10 mg/kg i.v.) did not alter basal respiratory insufflation pressure, but reduced the NANC bronchoconstrictor response to vagal stimulation in dose-dependent manner (with a maximal inhibition of 46.0 +/- 10.3%; mean +/- S.E. at 10 mg/kg) (P less than 0.02). Histamine itself also had a significant inhibitory effect on NANC responses with H1- and H2-blockade. The alpha-adrenoceptor antagonist phentolamine had no effect on the inhibitory response produced by alpha-MeHA, but the H3-receptor antagonist thioperamide blocked the inhibitory effect of alpha-MeHA. alpha-MeHA had no inhibitory effect on bronchoconstriction induced by exogenous substance P (5-25 micrograms/kg i.v.). We conclude that H3-receptors inhibit the release of transmitter from NANC nerves and that H3-receptors might play a role in regulation of neurogenic inflammatory responses in the airways.
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PMID:Histamine H3-receptors modulate nonadrenergic noncholinergic neural bronchoconstriction in guinea-pig in vivo. 248 90

1. The neurotransmitter of the non-cholinergic excitatory nerves in the rainbow trout stomach was identified on the basis of the pharmacological properties of the contractile responses to transmural stimulation (TMS) and nicotine. 2. TMS caused tetrodotoxin-sensitive contractions of rainbow trout stomach strips in a frequency-dependent manner (0.5-50 Hz). Atropine (1 microM) significantly decreased the contractile response to low-frequency stimulation (0.5-2 Hz), but did not affect that to high-frequency stimulation (3-20 Hz). 3. The atropine-resistant contractile response to TMS (20 Hz) was unaffected by hexamethonium (100 microM), phentolamine (5.4 microM), pyrilamine (1 microM), naloxone (1 microM) or substance P-induced desensitization. 4. 5-Hydroxytryptamine (5-HT, 3 nM-3 microM) caused atropine-resistant contractions in a concentration-dependent manner. In the presence of atropine, methysergide (1 microM) decreased the contractile responses to TMS and 5-HT. 5. Nicotine (3 microM-500 microM) induced atropine-resistant contractions that were completely abolished by tetrodotoxin or hexamethonium. Also methysergide inhibited the contractile responses to nicotine. 6. An acid extract of rainbow trout stomach exhibited atropine-resistant contractions that were decreased by methysergide, in both rainbow trout stomach and guinea-pig ileum longitudinal smooth muscle preparations. 7. The present results indicate that, in longitudinal muscle strips of the rainbow trout stomach, 5-HT is one of the mediators (neurotransmitters) of the non-cholinergic excitatory contractions induced by TMS and nicotine.
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PMID:5-Hydroxytryptamine is a possible neurotransmitter of the non-cholinergic excitatory nerves in the longitudinal muscle of rainbow trout stomach (Salmo gairdneri). 257 65

The cholinoceptive properties of dorsal horn neurons (lamina III-V) were investigated by means of intracellular recordings from the rat isolated spinal cord slice preparation. In half of the neurons investigated, acetylcholine (ACh) evoked a dose-dependent slow depolarization and increase in excitability; hyperpolarization was observed in 10% of neurons. Acetyl-beta-methylcholine (MCh) similarly depolarized 39% and hyperpolarized 25% of neurons tested; depolarization was also observed following bethanechol. Responses to the muscarinic agonists were abolished by atropine (10(-5) M). Nicotine depolarized 84% of tested neurons; dihydro-beta-erythroidine (5 x 10(-5) M) and (+)-tubocurarine (10(-6) M) antagonized this depolarization. ACh-, MCh- and nicotine-induced depolarizations, associated with changes in input resistance, were maintained in the presence of tetrodotoxin (10(-6) M). Substance P, as well as repetitive electrical stimulation of the dorsal root, also evoked depolarization in ACh-sensitive neurons. Atropine, but not (+)-tubocurarine, diminished responses to both substance P and dorsal root stimulation. These results indicate that dorsal horn neurons are ACh-sensitive and possess both muscarinic and nicotinic receptors. In addition, the parallel sensitivity of neurons to muscarinic agonists, substance P and dorsal root stimulation, as well as the parallel antagonistic effect of atropine, are supportive of a common ionic mechanism underlying the activation of muscarinic and substance P receptors.
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PMID:Cholinergic effects on spinal dorsal horn neurons in vitro: an intracellular study. 260 85


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