Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0043167 (pertussis)
 19,595 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Acetylcholine (Ach) was tested for its effect on calcium currents in primary cultures of embryonic rat hippocampal neurones. 10 microM Ach reversibly depressed the high voltage activated (HVA) Ca current and the effect was blocked by atropine. When GTP binding proteins (G-proteins) were irreversibly activated by intracellular perfusing the neurons with GTP[S], one short-lasting application of Ach permanently inhibited Ca currents. Alternatively, the transmitter was inactive when the cells were preincubated with pertussis toxin, which inactivates some G-proteins by catalyzing ADP ribosylation. Our results suggest that a G-protein mediates the inhibitory modulation of the HVA Ca current by muscarinic agonists.
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PMID:GTP-binding proteins mediate acetylcholine inhibition of voltage dependent calcium channels in hippocampal neurons. 254 6

Acetylcholine (Ach) was tested for its effect on calcium currents in primary cultures of embryonic rat hippocampal neurons. Ach reversibly depressed, in a dose-dependent way, the high voltage activated (HVA) Ca currents. The effect was antagonized by atropine. Our results suggest that a pertussis toxin (PTX)-sensitive GTP binding protein (G-protein) is involved in the signal transduction mechanism between the Ach receptor and the HVA Ca channel. Activating rather than depressive effects of Ach were observed on the low voltage-activated component of Ca currents. This effect was also antagonized by atropine but is not mediated by a PTX-sensitive G-protein.
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PMID:Opposing effects of acetylcholine on the two classes of voltage-dependent calcium channels in hippocampal neurons. 255 10

Acetylcholine (Ach) reversibly reduces the high voltage-activated (HVA) calcium (Ca) current in hippocampal neurons. Pretreatment of the cells with pertussis toxin (PTX) abolishes the Ach effect, suggesting that PTX-sensitive GTP-binding regulatory proteins (G-proteins) are involved in the signal transduction mechanism that links Ach receptor activation to inhibition of Ca channel activity. This effect is mimicked by intracellular application of the nonhydrolyzable GTP analog GTP gamma S. Intracellular application of purified G-proteins restored the response to Ach in PTX-treated cells. Furthermore, Ach inhibits the Ca current independently of the presence of cyclic AMP and of the protein kinase C inhibitor H-7 and neither does the Ach effect on the Ca current seem to be correlated to a transient increase in intracellular Ca. Our results suggest that activation of the alpha-subunit of the PTX-sensitive G-protein could directly modulate the HVA Ca channel without involving second messenger systems.
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PMID:Direct modulation of voltage-dependent calcium channels by muscarinic activation of a pertussis toxin-sensitive G-protein in hippocampal neurons. 256 Jan 67

Somatostatin, morphine, and opioids inhibit transmitter release at intact neuromuscular junctions between ciliary ganglion neurons and the choroidal smooth muscle of the chick eye. Somatostatin and morphine, however, have no effect on release from terminals on the striated muscle target of the ciliary ganglion, the iris. In neuronal terminals of both the choroid and the iris, a high-affinity Na+-dependent choline uptake-mediated ACh synthesis is present at hatching. Both tissues exhibit a basal release of 3H-ACh which is potentiated severalfold during a 5 minute incubation in 55 mM K+ Tyrodes. Fifty percent of the basal release and 100% of the stimulated release are Ca2+ dependent and probably mediated through N-like voltage-dependent Ca2+ channels. Co-incubation of the choroid with 10 microM morphine sulfate blocks approximately 90% of the stimulated release. The same effect is seen with 100 nM somatostatin, 10 microM dynorphin, and 100 microM met-enkephalin arginine phenylalanine. Preincubation of the excised choroid with pertussis toxin (200 ng/ml) reverses the inhibitory effects of both morphine and somatostatin. In contrast, 3H-ACh release from terminals in the striated iris is not affected by either morphine or somatostatin at micromolar levels. These results suggest that both opiate and somatostatin receptors are present in the choroid target and that they may act through a final common pathway to modulate ACh release via G proteins. Second messengers such as cyclic AMP or diacylglycerol do not appear to mediate these effects; neither increasing cAMP levels in terminals nor activation of protein kinase C affects evoked release or its inhibition by morphine or other neuromodulators. It is unclear whether endogenous neuromodulation occurs in this system, although somatostatin-like immunoreactivity can be demonstrated in terminals of choroid neurons.
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PMID:Opiate and peptide inhibition of transmitter release in parasympathetic nerve terminals. 256 61

In previous studies, we showed that cardiac muscarinic receptors (M2) are composed of two subgroups, M2 alpha and M2 beta, with different affinities for agonists and that the M2 alpha subgroup is coupled with inhibition of adenylate cyclase. We now studied which subgroup was responsible for the formation of inositol mono- (IP), bis- (IP2), tris- (IP3) and tetrakis- (IP4) phosphates in guinea pig heart. Carbachol (1 mM) significantly stimulated the formation of all four IPs in [3H]myoinositol-preloaded slices of guinea-pig ventricles. Acetylcholine (1 mM) also stimulated the formation of IP2, IP3 and IP4. However, oxotremorine (1 mM) only slightly stimulated the formation of IP2, and pilocarpine did not stimulate the formation of any IP. The pED50 values of carbachol for IP2 and IP3 formation were 3.76 and 4.23, respectively, which coincided with the pKd values of the low-affinity agonist binding site (L site) measured by competition of carbachol with [3H]quinuclidinyl benzilate [( 3H]QNB) binding while the pKd value for inhibition of adenylate cyclase coincided with the pKd value of the high-affinity agonist binding site (H site). Treatment of animals with pertussis toxin decreased the formation of IP2 and IP3 by carbachol to 66 and 54%, respectively, but resulted in complete inhibition of adenylate cyclase. These results suggested that muscarinic stimulation of the formation of IPs was manifested through a different receptor subgroup (M2 beta) and GTP binding protein different from those for inhibition of adenylate cyclase.
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PMID:The H-L subgroup of guinea-pig cardiac M2 receptors (M2 beta) regulates inositol phosphate formation. 258 43

Muscarinic acetylcholine receptor subtypes m1, m3 and m5 couple strongly to phosphatidylinositol turnover and hence to intracellular Ca2+ concentration via pertussis toxin (PTX) sensitive and insensitive G proteins. The m2 and m4 muscarinic receptor subtypes strongly inhibit adenylyl cyclase production via PTX sensitive G proteins. Additionally, the cardiac M2 receptor is closely coupled to a K+ current (IK.ACh). To characterize this functional diversity more completely, we measured the ACh-induced Ca2+ responses of cells transfected with the muscarinic receptor subtypes m1, m2, m3 and m4. As expected, cells transfected with m1 or m3 receptors exhibited large dose-dependent increases in Ca2+ in response to ACh application. Unexpectedly, cells transfected with m2 or m4 receptors also exhibited increases in Ca2+ in response to agonist application. The m2- or m4-coupled responses were smaller in amplitude, required higher concentrations of agonist and were much more sensitive to PTX treatment when compared to m1- or m3-coupled responses. We discuss this remarkable diversity of function in terms of the receptor subtype's coupling to G proteins.
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PMID:Diverse functions of muscarinic acetylcholine receptor subtypes. 269 20

Acetylcholine inhibits FSH-induced cAMP accumulation in cultured Sertoli cells from immature hamsters. This action of acetylcholine is mimicked by muscarinic cholinergic agonists with a rank order of carbachol greater than acetylcholine greater than arecoline greater than pilocarpine. The carbachol-induced inhibition of stimulated cAMP accumulation is blocked by atropine greater than pirenzepine but not by d-tubocurarine, indicating an apparent muscarinic receptor similar to that found in other peripheral tissues. The fact that pirenzepine is less effective as an inhibitor of the carbachol effect than atropine further defines the muscarinic effect as of the M2 subtype. The ability of carbachol to inhibit FSH-induced cAMP accumulation is blocked by pertussis toxin, which inhibits the action of the Ni inhibitory transducer of adenylate cyclase. These data indicate that cultured Sertoli cells from immature hamsters contain an M2 type muscarinic cholinergic receptor that is negatively coupled to the adenylate cyclase system through the inhibitory Ni transducer.
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PMID:Cholinergic inhibition of cAMP accumulation in Sertoli cells cultured from immature hamsters. 282 40

Acetylcholine (ACh) in low doses (0.1-1 microM) reversibly inhibits voltage-dependent activation of the "pacemaker" current, if, in isolated sino-atrial node cells. This action is brought about by a negatively-directed shift of the current activation curve, opposite to that due to catecholamines on the same current. The if inhibition is antagonized by atropine, indicating the involvement of muscarinic receptors. In cells incubated in pertussis toxin-containing solutions, if does not respond to ACh, suggesting that G-proteins mediate the ACh-induced if depression. Further, ACh can inhibit if following catecholamine-induced stimulation, but has a negligible effect on if stimulated by forskolin, a direct activator of adenylate-cyclase. Our results indicate that ACh acts on if by inhibiting basal adenylate-cyclase activity.
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PMID:Acetylcholine inhibits activation of the cardiac hyperpolarizing-activated current, if. 282 12

Muscarinic agonists can stimulate rather than inhibit cardiac muscle in some preparations. In left atria from hatched chicks, treatment with pertussis toxin reversed the membrane action of carbachol from hyperpolarization to depolarization and reversed the inotropic effect of carbachol from negative to positive. Acetylcholine also depolarized the membrane and increased the force of contraction in atria from pertussis-toxin-treated chicks although oxotremorine did not. These cholinergic responses were blocked by atropine but not by adrenoceptor antagonists, suggesting that they are mediated via muscarinic receptors and are not due to actions of endogenously released catecholamines. Muscarinic receptor stimulation leads to two distinct biochemical responses in chick atria: inhibition of adenylate cyclase and activation of phosphoinositide (PI) hydrolysis. The former is lost in atria from pertussis-toxin-treated chicks, whereas the PI response persists. The pharmacologic characteristics of the PI response resemble those of the depolarization and positive inotropic response. Both are insensitive to blockade by pertussis toxin, require high concentrations of carbachol, and are elicited by acetylcholine but not by oxotremorine. The present study suggests that muscarinic agonist-induced PI turnover may be responsible for the membrane depolarization and positive inotropic effects of carbachol and acetylcholine; that an increase in Na+ conductance underlies these responses; and that it is stimulated either by an increase of intracellular calcium mobilized by inositol triphosphate and/or by activation by protein kinase C.
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PMID:Pertussis toxin-insensitive phosphoinositide hydrolysis, membrane depolarization, and positive inotropic effect of carbachol in chick atria. 304 Feb 95

The control of M-current by muscarinic ACh receptors and luteinizing hormone releasing hormone (LHRH) receptors was studied in dialyzed frog sympathetic ganglion neurons. M-current was recorded in dialyzed cells without run-down or changes in its biophysical properties and could be reversibly suppressed by muscarine and teleost LHRH (t-LHRH). However, dialysis with internal solutions lacking ATP or substituting with APP(NH)P caused the loss of M-current, suggesting that dephosphorylation suppresses the activity of M-channels. M-current over-recovers after agonist addition and removal to a size 30% larger than control, as if latent channels are activated during the recovery. Dialysis of cells with the G-protein activators GTP gamma S, fluoride, and aluminum fluoride causes loss of M-current. G-protein activation by receptors was confirmed by dialysis with low concentrations of GTP gamma S in competition with GTP. This prevents the rapid loss of M-current, but addition of muscarine or t-LHRH caused irreversible loss of M-current, suggesting that both transmitter receptors do suppress M-current by activating a G-protein. Suppression of M-current was not affected by treatment with 0.1 microgram/ml pertussis toxin (IAP) for 24-48 hr. In addition, based on the lack of IAP-specific labeling of frog sympathetic neuron membrane proteins, no IAP-sensitive G-proteins are present in these cells. These results indicate that an IAP-insensitive G-protein couples muscarinic and LHRH receptors to the suppression of M-current.
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PMID:Muscarine and t-LHRH suppress M-current by activating an IAP-insensitive G-protein. 313 47


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