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 intracellular reaction mechanism underlying electrophysiological responses evoked by neurotensin (NT) was studied using Xenopus laevis oocytes injected with poly (A)+ messenger ribonucleic acid (mRNA) isolated from rat brains. 2. A few days after the injection of mRNA, oocytes were found to acquire sensitivity to NT and substance P. 3. Under voltage-clamp conditions (-60 mV), application of NT to mRNA-injected oocytes produced transient and oscillatory inward currents which began after a delay of several tens of seconds. These inward currents were accompanied by an increase in membrane conductance. 4. NT receptors on mRNA-injected oocytes showed essentially the same pharmacological properties as those of native NT receptors. 5. The NT response showed desensitization and was not readily recovered even after extensive washing of cells for more than 30 min. 6. NT response was suppressed when the muscarinic acetylcholine (ACh) response of the same cell, which was also induced by the same mRNA, was desensitized by a large dose of ACh. 7. NT response and ACh response showed many similarities: they were both inhibited by pertussis toxin and intracellular ethyleneglycol-bis-(beta-aminoethylether) N, N'-tetraacetic acid (EGTA), mimicked by intracellularly injected inositol 1, 4, 5-trisphosphate (InsP3), and suppressed when cell response to InsP3 was desensitized by a large dose of InsP3. Reversal-potential analyses indicated that both responses were mediated by an increase in membrane permeability to Cl-. 8. It is concluded that NT responses and muscarinic ACh responses of Xenopus oocytes induced by rat brain mRNA may most likely share a common reaction mechanism. The reaction sequence includes the activation of receptors, activation of inhibitory guanine nucleotide-binding regulatory protein, production of InsP3, intracellular Ca2+ mobilization, and increased membrane permeability to Cl-.
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PMID:Neurotensin and acetylcholine evoke common responses in frog oocytes injected with rat brain messenger ribonucleic acid. 244 67

The binding of substance P (SP) to receptors in peripheral tissues as well as in the CNS is subject to regulation by guanine nucleotides. In this report, we provide direct evidence that this effect is mediated by a guanine nucleotide-binding regulatory protein (G-protein) that is required for high-affinity binding of SP to its receptor. Rat submaxillary gland membranes bind a conjugate of SP and 125I-labeled Bolton-Hunter reagent (125I-BHSP) with high affinity (KD = 1.2 +/- 0.4 X 10(-9) M) and sensitivity to guanine nucleotide inhibition. Treatment of the membranes with alkaline buffer (pH 11.5) causes a loss of the high-affinity, GTP-sensitive binding of 125I-BHSP and a parallel loss of [35S]guanosine 5'-(3-O-thio)triphosphate ([35S]GTP gamma S) binding activity. Addition of purified G-proteins from bovine brain to the alkaline-treated membranes restores high-affinity 125I-BHSP binding. Reconstitution is maximal when the G-proteins are incorporated into the alkaline-treated membranes at a 30-fold stoichiometric excess of GTP gamma S binding sites over SP binding sites. Both Go (a pertussis toxin-sensitive G-protein having a 39,000-dalton alpha-subunit) and Gi (the G-protein that mediates inhibition of adenylate cyclase) appear to be equally effective, whereas the isolated alpha-subunit of Go is without effect. The effects of added G-proteins are specifically reversed by guanine nucleotides over the same range of nucleotide concentrations that decreases high-affinity binding of 125I-BHSP to native membranes.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Regulation of substance P receptor affinity by guanine nucleotide-binding proteins. 254 62

Intracellular recordings were made from neurons in the submucous plexus of the guinea-pig caecum. Muscarinic agonists (acetylcholine, bethanechol and muscarine) depolarized about 70%, and hyperpolarized about 30% of the submucous plexus neurons. Low concentrations of pirenzepine reversibly antagonized both responses. The measured dissociation constants (KD) of 10-30 nM for the depolarizations and 1-3 nM for the hyperpolarizations suggest that each response was mediated by muscarinic M1 cholinoceptors. The muscarinic depolarization and hyperpolarization were associated with a decreased and an increased conductance, respectively, and the reversal potential for the muscarinic responses varied as the potassium concentration varied, always being around the potassium equilibrium potential. In cells depolarized by muscarinic agonists these agents appeared to decrease a potassium conductance that could also be inactivated by substance P. In approximately 30% of the submucous neurons, the slow inhibitory postsynaptic potential, elicited in response to single or repetitive focal stimuli (1-10 pulses at 20-40 Hz), appeared to consist of a large component which was sensitive to the blocking action of idazoxan (100-300 nM) and a small component which was idazoxan-insensitive. The latter (muscarinic slow inhibitory postsynaptic potential) was completely abolished by pirenzepine. The concentrations of pirenzepine which caused a 50% depression ranged from 5 to 20 nM. The muscarinic slow inhibitory postsynaptic potential was increased in amplitude and duration by physostigmine (100-300 nM). The muscarinic slow inhibitory postsynaptic potential was accompanied by a decrease in membrane input resistance, and was reversed in polarity near the potassium equilibrium potential. When muscarine induced a hyperpolarization and/or focal stimulation elicited a muscarinic slow inhibitory postsynaptic potential in the presence of idazoxan (100-300 nM), the intracellular injection of guanosine 5'-O-(3-thiotriphosphate) produced a progressive membrane hyperpolarization during which the muscarinic hyperpolarizing responses were attenuated. It is concluded that the muscarine-induced reduction in potassium conductance is mediated through a muscarinic M1 receptor which has a relatively low affinity for pirenzepine. The muscarine-induced increase in potassium conductance is probably produced by the association of a guanine nucleotide-binding regulatory protein with another muscarinic M1 receptor that has a relatively high affinity for pirenzepine.
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PMID:Muscarinic excitation and inhibition of neurons in the submucous plexus of the guinea-pig caecum. 257 Mar 77