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)

The mechanism underlying the positive inotropic and chronotropic effects of capsaicin were investigated using the spontaneously beating guinea-pig atrium in vitro. Capsaicin induced a long-lasting stimulatory effect (threshold dose 10(-9) M). Tetrodotoxin, phentolamine, 6-OHDA, mepyramine plus cimetidine, methysergide-, indomethacin-, somatostatin- or morphine pretreatment and local treatment with capsaicin on the vagal nerves did not reduce the capsaicin response, while it was abolished up to 1 month after systemic capsaicin pretreatment. The capsaicin response was subject to a rapid tachyphylaxis. During capsaicin tachyphylaxis, the positive inotropic and chronotropic effects of noradrenaline, serotonin and histamine were unchanged. Various neuropeptides were investigated with regard to cardiac activity. Physalaemin, eledoisin and somatostatin had negative inotropic and chronotropic effects. Substance P, bombesin, kassinin, CCK-8 or PHI (up to 10(-6)M of each) did not cause any detectable response on the guinea-pig auricle, while the substance P antagonist [D-Arg, D-Pro, D-Trp, Leu]SP induced a long-lasting stimulation of heart activity, VIP also stimulated the heart. Various adenyl compounds were also tested. Adenosine, AMP, ADP, ATP and beta-, gamma-methylene ATP had negative chronotropic and inotropic effects, while alpha-, beta-methylene ATP induced a stimulatory response. During alpha-, beta-methylene ATP tachyphylaxis, the auricles still responded to capsaicin. The inhibitory effects of adenosine and ATP analogues were antagonized by theophylline and 8-p-sulfophenyl theophylline. Capsaicin induced a small release of labelled nucleotides from 3(H)-adenine-prelabelled atria from control, but not from capsaicin-pretreated animals.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Capsaicin-induced stimulation of the guinea-pig atrium. Involvement of a novel sensory transmitter or a direct action on myocytes? 620 51

Airway responsiveness is increased in a variety of airway diseases. To understand the mechanism of enhanced airway responsiveness, in particular as it pertains to asthma, animal models have been developed and extensively explored. The guinea pig and Basenji-greyhound dog are the best characterized animals showing airways hyperresponsiveness and appear to bear substantial resemblances to asthmatic human subjects. Challenge with bronchoconstrictive agonist results in bronchoconstriction and transient vascular leak. Both phenomena contribute to the degree of airway narrowing. Adenosine challenge tests not only the responsiveness of the airways, but also that of the airway effector cells such as the mastocyte. Bradykinin and tachykinin cause indirect airway narrowing, probably by liberation of leukotrienes. Responsiveness can be enhanced by immune and non-immune challenges. Ozone, Sephadex, various contractile agonists (leukotriene D-4, bradykinin, platelet-activating factor), as well as certain cytokines (IL-1, IL-2, TNF-alpha) can enhance airway responsiveness. Cyclooxygenase and lipooxygenase products appear to be involved. Allergen-induced hyperresponsiveness is associated with airway inflammation and appears to involve bradykinin and PAF acutely and growth of airway smooth muscle chronically.
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PMID:[Animal models of bronchial hyperreactivity]. 751 8

Effects elicited by adenosine and substance P on ventricular sensory endings of 14 dorsal root ganglion afferent neurons were studied in situ in anesthetized dogs. Sensory-field application of adenosine (1 microM) increased the activity of these neurons by 179%. Application of a nonspecific adenosine antagonist to epicardial sensory fields suppressed ongoing activity in all 14 neurons by 39%. Application of an A1- or A2-adenosine-receptor antagonist suppressed activity generated by 10 of these neurons by 44 and 59%, respectively. Adenosine applied after A1- or A2-receptor blockade increased activity in 10 neurons by 131 and 145%, respectively, indicating that A1- and A2-receptor effects were not additive. Application of substance P (1 microM) to identified sensory fields increased activity in 12 of these neurons by 169%, whereas application of a substance P-receptor antagonist reduced activity generated by these neurons by 75%. Myocardial ischemia increased activity of nine neurons associated with left ventricular sensory fields by 320%, an effect that was counteracted by the nonspecific adenosine-receptor antagonist. It is concluded that A1- and A2-adenosine receptors, as well as substance P receptors, are present on ventricular epicardial sensory nerve endings of dorsal root ganglion neurons that are tonically active during normal states, becoming further activated during ischemia.
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PMID:Ventricular sensory neurons in canine dorsal root ganglia: effects of adenosine and substance P. 754 44

Adenosine acts as a neuromodulator through A1 and A2 receptors. The adenosine analogs have been recognized, among other effects, as strong depressors of the locomotor activity by acting on striatal A2 receptors. Moreover, the A2a receptor subtype is exclusively expressed in the striatum. To elucidate at the cellular level the roles of adenosine in the basal ganglia, the anatomical and functional relationships of the A2 receptors with the dopamine D1 and D2 receptors were studied in the rat striatum. In situ hybridization histochemistry was used either in combination with retrograde labeling of striatonigral neurons to determine the projection site of A2a receptor expressing neurons, or on consecutive thin sections to address the putative coexpression of the A2a receptor with the D1 or D2 receptors in individual neurons. The A2a receptor is mainly expressed by neurons projecting to the globus pallidus and expressing also the dopamine D2 receptor and enkephalin, but very sparsely by neurons projecting to the substantia nigra that express the dopamine D1 receptor and substance P. We have further examined the regulatory effect of the A2 receptors on striatal gene expression using in situ hybridization histochemistry and quantitative autoradiography. Rats unilaterally depleted in dopamine by an unilateral 6-hydroxydopamine-induced lesion of the nigrostriatal pathway used as a model of Parkinson's disease subsequently received chronic injections of saline or the adenosine receptor antagonist caffeine. Intact rats were chronically treated with either saline, caffeine alone, caffeine with N-ethyl-carboxamidoadenosine (an equipotent A1 and A2 agonist), or caffeine with cyclohexyladenosine (a more selective A1 agonist).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Adenosine A2 receptors regulate the gene expression of striatopallidal and striatonigral neurons. 768 65

Capsaicin (1-3 microM) and electrical stimulation of mesenteric nerves in the presence of hexamethonium and guanethidine antidromically stimulate extrinsic sensory nerve fibers to produce a specific slow depolarizing response of myenteric neurons and a contractile response of muscles in the isolated guinea-pig ileum, mediated by release of substance P and acetylcholine. Adenosine (1-100 microM) inhibited the response to mesenteric nerve stimulation. Adenosine (10-100 microM) suppressed the contractile response to a threshold concentration of capsaicin (1 microM) while leaving the contractile response to a submaximal concentration of substance P (1 nM) and acetylcholine (0.1 microM) intact. Adenosine (1-10 microM) inhibited dose dependently the capsaicin 10 microM)-induced depolarization of myenteric neurons, but did not inhibit the depolarizing response to exogenous substance P. The adenosine P1 receptor antagonist, 8-phenyltheophylline (1-10 microM), antagonized the inhibitory effect of adenosine (1-10 microM) on the mechanical responses. We conclude that adenosine-induced prejunctional inhibition of the mechanical responses is mediated by adenosine P1 receptors.
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PMID:Adenosine inhibits efferent function of extrinsic capsaicin-sensitive sensory nerves in the enteric nervous system. 768 70

The influence of cervical and periarterial sympathectomy on endothelium-dependent and endothelium-independent relaxations of the mature rabbit carotid artery was studied in vitro. The responses to adenosine, vasoactive intestinal polypeptide and substance P in sympathectomized and control rabbit carotid artery rings were recorded and analyzed. The effects of endothelium removal were also investigated. The maximal relaxation achieved by substance P, which produces endothelium-dependent relaxation, was significantly inhibited in 3 weeks in postsympathectomy arterial preparations as compared to controls. Adenosine and vasoactive intestinal polypeptide, which produce endothelium-independent relaxation, elicited similar relaxation in all tissues. These results demonstrated that the response to substance P was impaired by cervical and periarterial sympathectomy. The decreased maximum response to substance P may be the result of a decreased NK-1 receptor subtype density or excitation/response coupling, or it may be due to an impaired production and/or liberation of endothelium-derived relaxing factor (EDRF).
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PMID:Altered endothelium-mediated relaxation by sympathectomy in isolated rabbit carotid artery rings. 864 97

The present work assesses the effects of the acute administration of adenosine on tachykinergic bronchoconstriction induced in different ways (exogenously administered capsaicin or substance P and vagal electrical stimulation) in anaesthetized and curarized guinea-pigs. Adenosine (30-3000 micrograms kg-1, i.v.) enhanced significantly and dose-relatedly the airway narrowing induced by a single dose of capsaicin (0.5-2 micrograms kg-1, i.v.), both in normal and in vagotomized animals. A smaller and less dose-dependent enhancement by the nucleoside of the pulmonary resistance increase induced by substance P (5-15 micrograms kg-1, i.v.) was observed. This effect was almost completely prevented by the H1 antagonist diphenhydramine (1 mg kg-1, i.v.), which also unmasked an inhibitory action of adenosine at the highest doses. Diphenhydramine, on the contrary, did not significantly modify the potentiation by adenosine of capsaicin-mediated bronchoconstriction. Finally, the nucleoside dose-dependently inhibited the atropine-resistant bronchospasm following vagal electrical stimulation. The use of the selective adenosinic agonists R-N6-[2-phenylisopropyl]adenosine (1-100 micrograms kg-1, i.v.) and 5'-N-methylcarboxamidoadenosine (1-100 micrograms kg-1, i.v.) before the administration of capsaicin, revealed the ability of the first to reproduce the enhancement induced by adenosine, while the second had an inhibitory effect. It is concluded that adenosine has both excitatory and inhibitory modulatory effects on airway responsiveness to excitatory non-adrenergic non-cholinergic (e-NANC) stimuli. The excitatory effects, revealed with substance P and capsaicin, support the hypothesis that adenosine may play a role as an asthma mediator.
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PMID:Effects of adenosine on NANC bronchoconstriction in anaesthetized guinea-pigs. 879 95

At the turn of this century, it was proposed that ischemic cardiac pain might be related to distension of the ventricular wall ("mechanical hypothesis"). Three decades later, it was hypothesized that ischemic pain might be elicited by the intramyocardial release of pain-producing substances induced by ischemia ("chemical hypothesis"). Studies carried out in the past 10 years have given strong support to the chemical hypothesis, because they have consistently shown that adenosine is a mediator of ischemic cardiac pain. Adenosine-induced ischemic cardiac pain is mediated primarily by stimulation of A1 receptors located in cardiac nerve endings and is potentiated by substance P. Conversely, the magnitude and rate of left ventricular dilation during ischemia do not predict the severity of angina. It is worth noting, however, that stretching of epicardial coronary arteries appears to potentiate the severity of angina caused by myocardial ischemia. The nervous activity generated by myocardial ischemia is modulated in intrinsic cardiac, mediastinal, and thoracic ganglia. Then it is further modulated in the central nervous system and projects bilaterally to the cortex, as demonstrated in humans by positron emission tomography, where it is decoded as a painful sensation. The causes responsible for the lack of angina during myocardial ischemia are probably different in patients who present both pain-free and painful myocardial ischemia, in patients with predominantly painless ischemia, and in diabetic patients.
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PMID:New look to an old symptom: angina pectoris. 939 81

The influence of adenosine and selective A1 and A2 agonists and antagonists was investigated on the cholinergic and the excitatory non-cholinergic (e-NC) contractions induced by electrical field stimulation in the guinea-pig bronchi. Adenosine (10 nM-1 mM) induced a concentration-dependent inhibition of the e-NC contraction (EC50 = 90 +/- 14 microM), whereas the cholinergic peak was only slightly affected. Preincubation of the tissue with the adenosine uptake blocker dipyridamole (10 microM) significantly shifted the concentration-inhibition curve to adenosine to the left (EC50 = 10 +/- 1 microM), suggesting an interaction with extracellular adenosine receptors of A1 and/or A2 subtype. To characterize the receptor type involved in this effect, selective adenosine derivatives were studied. The agonist to both A1 and A2 adenosine receptors, 5'-N-ethylcarboxamidoadenosine (NECA) was more potent than the selective A1 agonist, (-)-R-6-phenylisopropyladenosine (R-PIA), in inhibiting the e-NC contraction (EC50 = 0.10 +/- 0.04 and 0.60 +/- 0.12 microM, respectively, with a maximal inhibition of 70 and 45%, respectively). The concentration-response curve to NECA was shifted to the right by the A2 receptor selective antagonist 3,7-dimethyl-1-propargylxanthine (DMPX) (10 microM) (EC50 = 1.4 +/- 0.5 microM) as well as by the specific A1 receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX) (10 microM) (EC50 = 0.7 +/- 0.3 microM). The inhibitory effect induced by the association of both antagonists, DPCPX and DMPX, was considerably potentiated (EC50 > 22 +/- 2.5 microM). The effect of R-PIA was also shifted to the right by DPCPX (EC50 = 8.2 +/- 1.6 microM) but was not modified by DMPX. The contractile response to exogenous substance P was unaffected by NECA pretreatment (0.3 microM). Altogether, these results suggest that adenosine-induced inhibition of e-NC contraction of guinea-pig bronchi is mediated through activation of both A1 and A2 adenosine receptors linked to inhibition of the release of neuropeptides from C-fibre nerve endings.
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PMID:Adenosine reduces airway excitatory non-cholinergic (e-NC) contraction through both A1 and A2 adenosine receptor activation in the guinea pig. 944 16

Adenosine and ATP exert multiple influences on pain transmission at peripheral and spinal sites. At peripheral nerve terminals in rodents, adenosine A1 receptor activation produces antinociception by decreasing, while adenosine A1 receptor activation produces pronociceptive or pain enhancing properties by increasing, cyclic AMP levels in the sensory nerve terminal. Adenosine A3 receptor activation produces pain behaviours due to the release of histamine and 5-hydroxytryptamine from mast cells and subsequent actions on the sensory nerve terminal. In humans, the peripheral administration of adenosine produces pain responses resembling that generated under ischemic conditions and the local release of adenosine may contribute to ischemic pain. In the spinal cord, adenosine A receptor activation produces antinociceptive properties in acute nociceptive, inflammatory and neuropathic pain tests. This is seen at doses lower than those which produce motor effects. Antinociception results from the inhibition of intrinsic neurons by an increase in K+ conductance and presynaptic inhibition of sensory nerve terminals to inhibit the release of substance P and perhaps glutamate. There are observations suggesting some involvement of spinal adenosine A2 receptors in pain processing, but no data on any adenosine A3 receptor involvement. Endogenous adenosine systems contribute to antinociceptive properties of caffeine, opioids, noradrenaline, 5-hydroxytryptamine, tricyclic antidepressants and transcutaneous electrical nerve stimulation. Purinergic systems exhibit a significant potential for development as therapeutic agents. An understanding of the contribution of adenosine to pain processing is important for understanding how caffeine produces adjuvant analgesic properties in some situations, but might interfere with the optimal benefit to be derived from others.
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PMID:Adenosine receptor activation and nociception. 965 Aug 42


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