Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P20366 (substance P)
 21,176 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recent Neurobiological (Neurophysiological, Histochemical, Neurochemical and behavioural studies) data have indicated that the analgesic effects of morphine may, at least in part, be explained by two modes of action. A--Morphine has a direct depressive action at a spinal level on the activity of neurones of the grey matter of the dorsal horn which run towards the higher centres of the encephalon. These effects are exerted preferentially on activities induced by the activity of fine non-myelinized fibres (C). These mechanisms are discussed taking into account recent data concerning polypeptides (substance P and encephalins). B--Morphine acts at the level of the brain stem (periaqueductal grey matter, raphian nucleus, etc.) reinforcing the activity of descending bulbo-spinal pathways which block the transmission of painful messages within the cord.
 ...
PMID:[Morphine analgesia: neurobiologic data]. 2 30

The effect of Substance P infused intracerebrally via chronically implanted electrode-cannulae on self-stimulation induced from the same site was studied in rats. Substance P caused a significant depression of self-stimulation at 60 and 120 microgram/rat. Morphine infused into this site also caused significant depression of self-stimulation, but the doses were considerably lower than those of Substance P (5 and 10 microgram/rat). Pretreatment with naloxone, a narcotic antagonist, significantly antagonized the effects of Substance P on self-stimulation. It is proposed that Substance P modulates self-stimulation by the release of an endogenous morphine-like substance, but the possibility of a direct effect of Substance P was not ruled out.
 ...
PMID:Effect of substance P on medial forebrain bundle self-stimulation in rats following intracerebral administration. 59 92

Rats were trained to discriminate morphine (7.5 mg/kg, IP) from saline in a two bar positively reinforced lever pressing paradigm on a FR4 schedule. Morphine (IP) showed a naloxone reversible dose-related generalization to the training dose. [DAla2]-Methionine enkephalinamide (DAE) at 1 mg/kg and Substance P (SP) at 0.1 and 0.25 mg/kg showed vehicle appropriate responding after IP injection. DAE (5 mg/kg) disrupted responding completely; SP (0.5 and 0.1 mg/kg) disrupted responding in 50% of the rats. The disruption caused by IP injection of DAE was not naloxone reversible. Intraventricular injection of morphine (5 microgram/rat) and DAE (5 microgram/rat) produced generalization to the opiate cue. The effect of DAE was reversed by naloxone (1 mg/kg, SC). SP (500 and 750 ng/rat, IVT) produced saline-like responding; 1 microgram/rat disrupted responding completely. These data demonstrate that morphine and enkephalin, but not Substance P, share similar discriminative properties.
 ...
PMID:Brief communication. Generalization of [DAla2]-enkephalinamide but not of substance P to the morphine cue. 70 49

The effects of intracerebroventricular administration of morphine, the selective mu-agonist DAMGO, the delta-agonist DPDPE, the kappa-preferring peptide dynorphin A(1-13) and the kappa-agonist U50,488H on locomotor behaviour in the guinea pig were investigated. Morphine (total dose = 0.01, 0.1, 1, 10, 200 nmol), DAMGO and DPDPE (total dose = 0.1, 1, 10, 100 nmol of each) produced piloerection and sedation, indicating that the responses of guinea pigs to mu- and delta-opioid agonists differed from those of rats and mice. In contrast, U50,488H (total dose = 10, 100 nmol) and dynorphin A(1-13) (total dose = 100 nmol) produced increased locomotor activity which was attenuated by pretreatment with naloxone and norbinaltorphimine, thus confirming the involvement of kappa-opioid receptors. Furthermore, pretreatment with spantide, baclofen, muscimol, bicuculline, MK-801, raclopride and atropine also inhibited the U50,488H-induced locomotor activity, suggesting the involvement of GABA, dopamine, excitatory amino acids, substance P and acetylcholine in this response.
 ...
PMID:Effects of intracerebroventricularly administered mu-, delta- and kappa-opioid agonists on locomotor activity of the guinea pig and the pharmacology of the locomotor response to U50,488H. 135 40

1. Goblet cell secretion in guinea-pig airways is under neural control. Opioids have previously been shown to inhibit neurogenic plasma exudation and bronchoconstriction in guinea-pig airways. We have now examined the effects of morphine and opioid peptides on tracheal goblet cell secretion induced by either electrical stimulation of the cervical vagus nerves, exogenous capsaicin, or acute inhalation of cigarette smoke. The degree of goblet cell secretion was determined by a morphometric method and expressed as a mucus score which is inversely related to mucus discharge. 2. Morphine, 1 mg kg-1, completely blocked goblet cell secretion induced by electrical stimulation of the vagus nerves. Morphine also inhibited the response to cigarette smoke given either at a low dose (10 breaths of 1:10 diluted in air), which principally activates cholinergic nerves, or at a high dose (20 breaths of undiluted), which activates capsaicin-sensitive sensory nerves, by 100% and 73% respectively. In contrast, morphine had no significant inhibitory effect on capsaicin-induced goblet cell secretion. The inhibitory effect of morphine was reversed by naloxone. 3. Selective mu- or delta-opioid receptor agonists, [D-Ala2, NMePhe4, Glyol5]enkephalin (DAMGO) or [D-Pen2, D-Pen5]enkephalin (DPDPE) respectively, caused a dose-related inhibition of low dose cigarette smoke-induced goblet cell discharge, with DPDPE more potent than DAMGO. A kappa-receptor agonist, trans-3,4-dichloro-N-methyl-N-(2-(1-pyrollidinyl)cyclohexyl) benzeneacetamine (U-50,488H), had no inhibitory effect. DPDPE had no inhibitory effect on goblet cell secretion induced by exogenous methacholine. 4. DAMGO dose-dependently blocked the response to high dose cigarette smoke with a maximal inhibition of 95% at 2 x 10(-7) mol kg-1. Neither DPDPE nor U-50,488H had any significant inhibitory effect. The increase in goblet cell secretion induced by exogenous substance P was not affected by DAMGO.5. We conclude that opioids inhibit neurally-mediated goblet cell secretion via actions at prejunctional delta and mu-receptors on cholinergic nerves and at mu-receptors on sensory nerve endings, and that capsaicin activation of sensory nerves is via a different mechanism from that of electrical or cigarette smoke activation.
 ...
PMID:Differential inhibitory effects of opioids on cigarette smoke, capsaicin and electrically-induced goblet cell secretion in guinea-pig trachea. 137

The nature of the interaction between spinally administered opioid and alpha-2 agonists was investigated using the substance P behavioral test in mice. Morphine and agonists which more selectively activate mu or delta opioid receptors were co-administered intrathecally with direct and indirect acting adrenergic agonists norepinephrine, cocaine or clonidine and the behavioral responses to intrathecally coadministered substance P were evaluated. The ED50 values for agonists administered separately and concurrently were computed and drug interactions were evaluated using isobolographic analyses. After separate administration, all the opioid and adrenergic agonists inhibited the substance P-induced behavioral responses. Upon coadministration of opioid and adrenergic agonists, a multiplicative interaction was observed between morphine or the delta agonist D-Pen2-D-Pen-5-enkephalin and the adrenergic agonists. Additive or antagonistic interactions were found between the mu agonist Tyr-D-Ala-NMe-Phe-Gly(ol) and the same adrenergic agonists. The opioid antagonist naloxone and the alpha-2 adrenergic antagonist idazoxan were given as intrathecal pretreatments at doses chosen to shift the dose-response curves of their corresponding agonist (given alone) 4- to 10-fold to the right; this always resulted in a smaller, but significant (2- to 4-fold) shift in the dose-response curve of the other agonist given alone. Intrathecal pretreatment with naloxone or idazoxan altered some interactions between the opioids and clonidine. Although naloxone blocked completely the multiplicative interaction between morphine and clonidine, idazoxan did not. Both naloxone and idazoxan changed the antagonistic interaction between Tyr-D-Ala-NMe-Phe-Gly(ol) and clonidine to a multiplicative interaction. Neither antagonist blocked the multiplicative interaction between D-Pen2-D-Pen5-enkephalin and clonidine. These results suggest that: 1) interactions between opioid and adrenergic agonists in mouse spinal cord are mediated by delta and alpha-2 receptor subtypes; 2) the synergistic interaction between morphine and alpha-2 adrenergic agonists may involve action at delta opioid receptors; and 3) antagonist action on these drug interactions is complex.
 ...
PMID:Spinal interactions between opioid and noradrenergic agonists in mice: multiplicativity involves delta and alpha-2 receptors. 137 95

It is generally accepted that morphine acts presynaptically to inhibit substance P (SP) release from afferent terminals in the trigeminal nucleus. Recent studies, however, provide evidence that opioids produce both inhibitory and excitatory effects on SP release which are concentration- and receptor subtype-dependent. In the present study, we have examined a wide range of morphine concentrations on K(+)-evoked SP release from rat trigeminal nucleus caudalis slices. Immunoreactive SP was measured in perfusates. Morphine produced multiphasic effects on K(+)-evoked SP release without affecting basal release. A very low nanomolar concentration (1 nM) suppressed release, higher nanomolar concentrations (100-300 nM) facilitated release, a low micromolar concentration (3 microM) suppressed release, and a higher micromolar concentration (30 microM) facilitated release. These effects were abolished by opioid receptor blockade with naloxone (30 nM). Thus, morphine produces a complex bi-directional modulation of SP release from TNC which is concentration- and possibly receptor subtype-dependent.
 ...
PMID:Multiphasic effect of morphine on the release of substance P from rat trigeminal nucleus slices. 137 46

Morphine (MOR) produces a concentration-dependent multiphasic effect (inhibitions and facilitations) on K(+)-evoked substance P (SP) release from rat trigeminal nucleus slices. In this study, we tested the action of selective opioid receptor antagonists on this multiphasic effect of MOR. 1 nM MOR produced an inhibition of K(+)-evoked release of SP that was affected only by the selective mu 1-opioid receptor antagonist naloxonazine (1 nM). MOR at 100 nM elicited an increase in SP release which was abolished selectively by the mu-opioid receptor antagonist, beta-funaltrexamine (beta-FNA; 20 nM) and attenuated by the delta-opioid receptor antagonist, ICI 174,864 (0.3 microM). 3 microM MOR produced an inhibition of SP release that was reversed only by ICI 174,864 (0.3 microM). MOR at even higher concentrations (30 microM) produced an enhancement of SP release that was reversed selectively by 3 nM n-binaltorphimine (n-BNI; 3 nM), a kappa-opioid receptor antagonist. In slices pretreated with 20 nM beta-FNA and in the presence of 0.3 microM ICI 174,864 (mu- and delta-opioid receptor blockade), both 100 nM and 3 microM MOR elicited a strong facilitation of K(+)-evoked SP release which was sensitive to 3 nM n-BNI. Thus, the increase in SP release produced by 100 nM may be mediated by the simultaneous stimulation of beta-FNA-sensitive mu- and excitatory delta-opioid receptors whereas the facilitation of SP release induced by 30 microM MOR could be due to the activation of kappa-opioid receptors. 1 nM and 3 microM MOR may inhibit SP release by stimulating naloxonazine-sensitive mu 1- and inhibitory delta-opioid receptors, respectively.
 ...
PMID:Morphine produces a multiphasic effect on the release of substance P from rat trigeminal nucleus slices by activating different opioid receptor subtypes. 137 47

The experiments examine the actions of morphine and opioid peptides on the responses evoked by electrical field stimulation or by acetylcholine (ACh) and substance P (SP) in guinea-pig bronchial strip chain. Electrical field stimulation evoked a biphasic contraction, consisting of a cholinergically mediated fast contraction followed by a non-cholinergically mediated slow contraction. Morphine and opioid peptides caused a concentration-dependent inhibition in the height of the non-cholinergic contraction. The order of inhibitory activity was BW443C greater than dynorphin greater than morphine greater than beta-endorphin greater than leucine-enkephalin greater than methionine-enkephalin. Cholinergically mediated contractions were less potently inhibited by these opioids. Submaximal contractions of bronchial muscle evoked by exogenous ACh (2 microM) or SP (0.2 microM) were not inhibited by morphine (100 microM) or opioid peptides (3-10 microM), rather, they were augmented. The results indicate that in guinea-pig isolated bronchial muscle, morphine and opioid peptides can selectively inhibit excitatory non-cholinergic neurotransmission via prejunctional opioid receptors.
 ...
PMID:Morphine and opioid peptides selectively inhibit the non-cholinergically mediated neurogenic contraction of guinea-pig isolated bronchial muscle. 169 28

Recent evidence suggests that opioids might have excitatory as well as inhibitory actions on neurones. Since substance P (SP) has been implicated in opioid withdrawal, the present experiment was conducted to determine whether SP was released by morphine or morphine withdrawal. Sagittal brain slices and a 2 cm piece of ileum from 5 guinea-pigs were placed in Krebs solution. Morphine 1 microM, produced significant release of SP-like immunoreactivity (SP-LI) within 2 min from brain slices but release from ileum preparations was variable. Naloxone 1 microM, added 5 min after morphine, did not produce significantly greater increase in concentration of SP-LI. It is concluded that morphine releases SP from guinea-pig brain slices.
 ...
PMID:Morphine produces release of substance P-like immunoreactivity from guinea-pig central nervous system. 170 71


1 2 3 4 5 6 7 8 9 Next >>