Evidence against prostaglandin E having a physiological role in acetylcholine liberation from Auerbach's plexus of guinea-pig ileum.

The effect of INDO, a PGE synthesis inhibitor, on ACh output from Auerbach's plexus of guinea-pig ileum was investigated. INDO (15-45 mum/ml) failed to alter significantly either spontaneous ACh output or ACh output induced by field stimulation. It is concluded that PGE plays no physiological role in ACh liberation from this tissue.     

Desensitization of the muscarinic receptor of bullfrog atrial muscle

Summary The muscarinic ACh receptors, which hyperpolarize the resting membrane and also depress the action potential of bullfrog atrial muscle, show desensitization to the action of ACh. This suggests that the molecular mechanism of these muscarinic ACh receptor-ionic channel (voltage-dependent) complexes is comparable to that of the nicotinic ACh receptor-ionic channel (voltage-independent) complex of the end-plate.Acknowledgment. This work was supported by a grant-in-aid for Scientific Research from the Ministry of Education, Science and Culture of Japan.     

Über die Abhängigkeit der Acetylcholinwirkung von der äusseren Ca-Konzentration bei isolierten Meerschweinchenvorhöfen

Summary In the left auricles of guinea-pigs, Ca-ions have an antagonistic effect on the negative inotropic action of ACh. This effect is independent of the degree of shortening of the action potential by ACh.     

Über den Einfluss von Desoxycorticosteron auf Kontraktur und Kaliumfreisetzung durch Acetylcholin an der innervierten und denervierten Skelettmuskulatur

Summary The release of potassium ions from striated muscle, and the changes in mechanical tension developed by the gastrocnemius muscle on intraarterial injection of ACh, were investigated by isolated perfusion of the hind limbs in cats. The reaction of the normal innervated and chronically denervated muscle in the same animal were compared before and during perfusion with 2·10^–4 M/l desoxycorticosterone glucoside (DCG). The following results were obtained: after perfusion with DCG no change in the spontaneous release of potassium ions occurred neither on the innervated nor on the denervated muscle. The potassium release following intra-arterial injections of various doses of ACh was significantly reduced on innervated and denervated muscle. On the denervated muscle there was also a considerable reduction of the height of contractures caused by ACh administration. The results make it probable that DCG acts by an inhibition of depolarisation in the same way asd-tubocurarine.     

Effects of a new cholecystokinin antagonist (GE 410) on the smooth muscle of the guinea pig ileum

Suc-Tyr-(SE)-Met-Gly-Trp-Met-Asp-beta-phenethylamide (GE 410) competitively antagonized the contractions of smooth muscle strips from guinea pig ileum (pA2 = 7.6, n = 0.95) induced by cholecystokinin-octapeptide (CCK8). GE 410 inhibited the electrically-induced cholinergically mediated contractile responses and the [3H]ACh release in the ileum, as well as the CCK-stimulated electrical contractile responses and the [3H]ACh release in the cholinergic nerve terminals. The results suggest the existence of CCK-receptors not only in the smooth muscles but also on the neurons.     

Changes with hypertension and maturation in the response of stomach fundus to acetylcholine

The purpose of these experiments was to compare the contractile response to ACh of stomach fundal strips from hypertensive (SHR) and normotensive (WKY) rats during the development of hypertension. The results indicate that the reactivity to ACh is the same in fundal strips from young SHR and WKY rats; however, with maturation strips from WKY rats undergo a reduction in responsiveness which does not occur in the SHR. Therefore, strips from older SHR rats are more reactive to ACh than are those from age matched WKY rats.     

Changes with hypertension and maturation in the response of stomach fundus to acetylcholine

Summary The purpose of these experiments was to compare the contractile response to ACh of stomach fundal strips from hypertensive (SHR) and normotensive (WKY) rats during the development of hypertension. The results indicate that the reactivity to ACh is the same in fundal strips from young SHR and WKY rats; however, with maturation strips from WKY rats undergo a reduction in responsiveness which does not occur in the SHR. Therefore, strips from older SHR rats are more reactive to ACh than are those from age matched WKY rats.Acknowledgment. The authors wish to acknowledge the assistance of Mark Kunneman and Elaine Hughes. This work was supported by the following grants: American Heart Association (Texas Affiliate) and National Institutes of Health HL 23815, HL 25349 and HL 24585.     

Cardioactive peptides of the CNS of the pulmonate snailLymnaea stagnalis

Summary In the pulmonate snailLymnaea stagnalis the cardioactive effects (tested on isolated auricles) of acetylcholine (ACh), 5-hydroxytryptamine (5-HT), the bivalve tetrapeptide FMRFamide, and of chromatographically separated snail brain substances have been established. Besides ACh and 5-HT, in brain extracts, small FMRFamide-like and large cardioexcitatory peptides were found.     

Lack of participation of cytoplasmic choline in the synthesis of acetylcholine in the striatal synaptosomes of the rat]

Synaptosomes prepared from Rat striatum were loaded with (14C) choline at 0 degrees C in the course of a 60 min. preincubation. After the removal, by washing, of the extracellular molecules, synaptosomes were incubated 5 min. at 37 degrees C in the presence of (3H) choline. The measurement of the amounts of (3H) ACh and of (14C) ACh formed allowed us to conclude that the acetylation of the molecules of choline was directly coupled to their passage through the synaptosomal membrane.     

Effects of a new cholecystokinin antagonist (GE 410) on the smooth muscle of the guinea pig ileum

Summary Suc-Tyr-(SE)-Met-Gly-Trp-Met-Asp--phenethylamide (GE 410) competitively antagonized the contractions of smooth muscle strips from guinea pig ileum (pA₂=7.6, n=0.95) induced by cholecystokinin-octapeptide (CCK8). GE 410 inhibited the electrically-induced cholinergically mediated contractile responses and the [³H]ACh release in the ileum, as well as the CCK-stimulated electrical contractile responses and the [³H]ACh release in the cholinergic nerve terminals. The results suggest the existence of CCK-receptors not only in the smooth muscles but also on the neurons.     

Arguments in favor of the extramitochondrial origin of the acetyl radical of acetylcholine synthetized in rat striatum synaptosomes]

Synaptosomes prepared from Rat striatum were loaded with (2-14C) pyruvate at 0 degree C, in the course of a 1 hr. preincubation. When temperature was raised to 37 degrees C, the intra-synaptosomal (2-14C) pyruvate gave rise to 14CO2 but not to (14C) ACh. These results exclude a mitochondrial origin of the acetyl moiety of ACh.     

Formation of the neuromuscular junction in cultures of rat embryonic cells]

The morphological evidence of the primary nerve muscle contacts are described. They consist of areas of cholinesterase activity (detected histochemically) localized on the myotube membranes and of mutiple clusters of ACh receptors whose 125I-alpha-bungarotoxin binding sites are revealed by radio-autography. After the stage of the primary nerve muscle contacts, some of which seem transient, characteristic neuromuscular junctions appear. These neuromuscular junctions which possess subneural infoldings are similar to the end-plates of the Rat in vivo.     

Butanol extracts from myelin fragments. IV. Some interactions between 5-hydroxytryptamine and other neurotransmitters binding

Summary To examine the interaction between 5-HT and other neurotransmitters binding to the butanol extracts from myelin, double labelling experiments were done. The binding peaks of C¹⁴. ACh and NA were clearly different from that of H³. 5-HT. At 5×10^–7 M, binding of 5-HT, ACh, NA, GABA and DA was 62.7, 2.3, 7.0, 5.8 and 1.9 nmoles/mg protein, respectively. These results suggest that the 5-HT binding components of myelin butanol extracts may have high selectivity and specificity.     

Sodium concentration and the effect of angiotensin II on iieal smooth muscle

Zusammenfassung Die kontraktile Reaktion des isolierten Meerschweinchen-Ileums auf Angiotensin II variierte direkt mit der Natriumkonzentration der Nährflüssigkeit, nicht aber bei ACh; Atropin (10^–6 g/ml) reduzierte die Wirkung auf Angiotensin um 60–70% und hob die Wirkung auf äquivalente Mengen von ACh auf. In atropinhaltiger Ringerlösung potenzierte ein hoher Natriumgehalt (+ 30 meq./l) die Reaktion auf Angiotensin zehnfach.     

Intravenous thyrotropin releasing hormone (TRH) enhances the excitatory actions of acetylcholine (ACh) on rat cortical neurons

Summary I. v. administered TRH (1.25-10 mg/kg) enhanced the excitatory actions of iontophoretically applied ACh on spontaneously active cerebral cortical neurons of pentobarbital-anaesthetized rats. These observations are consistent with the hypothesis of a cholinergic-link in the anti-anaesthetic actions of exogenously administered TRH.     

Chronic gestational exposure to ethanol causes insulin and IGF resistance and impairs acetylcholine homeostasis in the brain

In fetal alcohol syndrome (FAS), cerebellar hypoplasia is associated with impaired insulin-stimulated survival signaling. This study characterizes ethanol dose-effects on cerebellar development, expression of genes required for insulin and insulin-like growth factor (IGF) signaling, and the upstream mechanisms and downstream consequences of impaired signaling in relation to acetylcholine (ACh) homeostasis. Pregnant Long Evans rats were fed isocaloric liquid diets containing 0%, 2%, 4.5%, 6.5%, or 9.25% ethanol from gestation day 6. Ethanol caused dose-dependent increases in severity of cerebellar hypoplasia, neuronal loss, proliferation of astrocytes and microglia, and DNA damage. Ethanol also reduced insulin, IGF-I, and IGF-II receptor binding, insulin and IGF-I receptor tyrosine kinase activities, ATP, membrane cholesterol, and choline acetyltransferase (ChAT) expression. In vitro studies linked membrane cholesterol depletion to impaired insulin receptor binding and insulin-stimulated ChAT. In conclusion, cerebellar hypoplasia in FAS is mediated by insulin/IGF resistance with attendant impairments in energy production and ACh homeostasis. Received 4 May 2006; received after revision 13 June 2006; accepted 20 June 2006     

Actions de la néostigmine,du D.F.P. et du 3318 CT sur la sensibilité du rectus de grenouille aux esters acétique,propionique et butyrique de la choline

Summary The potentiating effects of Neostigmine, D.F.P. and 3318 CT (a selective true cholinesterase inhibitor) on acetylcholine (ACh), propionylcholine (PrCh), butyrylcholine (BuCh) and amyltrimethylammonium (AmT), have been studied using the frog's rectus abdominis. Neostigmine increases the actions of the three esters much more than that of AmT. Low concentrations of D.F.P. potentiate maximally BuCh but have practically no effect on ACh, PrCh, and AmT. 3318 CT potentiates AcCh and PrCh but inhibits BuCh and AmT.These results indicate the specificity of the hydrolysis of pharmacologically active doses of BuCh, on the one hand, of AcCh and PrCh, on the other hand, by different enzymes or the frog's rectus.Results obtained with high concentrations of D.F.P. and with association of the different anticholinesterases indicate that a maximal or nearly maximal potentiation of one of these esters is already obtained with the specific inhibitor concerned; the supplementary inhibition of the non-specific enzymes thus appears to have no or only a poor effect.     

The blood vessels of cephalopods. A comparative morphological and functional survey

Summary The distinctive structural and functional features of the highly specialized blood vessel types (blood sinus, veins, aortae, arteries) of cephalopods are characterized in a comparative survey. Histochemical and physio-pharmacological results indicate a dual neuroregulation of the vessel wall but, however, show contrary effects of the neurotransmitter candidates, catecholamines, serotonin (5-HT) and ACh, on arteries and veins. The spontaneous pulsatile activity of the propulsive veins seems to be partly myogenic but also directly dependent on a dense cholinergic innervation of the sarcosome-rich obliquely striated myocytes.     

Nervous control of smooth muscle by transmitters,cotransmitters and modulators

Conclusion The part played by peripheral neuroeffector control mechanisms has been underestimated. These are additional to central and ganglionic control mechanisms and are much more elaborate than originally thought. While the classical view is that the autonomic nervous system consists largely of antagonistic cholinergic and adrenergic nerves, about sixteen putative neurotransmitters have been proposed in autonomic nerves in the past few years, including various monoamines, polypeptides, purines and amino acids. Modulatory transmitter mechanisms have also been recognized, including prejunctional inhibition or enhancement of transmitter release, postjunctional modulation of transmitter action, and the secondary involvement of locally synthesized hormones and prostaglandins. The existence of more than one transmitter substance in some nerves is now widely recognized, and suggestions have been made about the ways that this can lead to differential peripheral control mechanisms at nerve terminals themselves. The cotransmitters always have synergistic actions on postjunctional effector cells, but two different operating mechanisms are postulated. 1) If both substances are stored in the same vesicles (for example, ACh or NA with ATP), release is closely parallel at all impulse frequencies. Upon release, the cotransmitter, in addition to having a direct action on postjunctional cells, may facilitate the action of the other transmitter and/or act as an inhibitor of its release. Differential actions at different impulse frequencies are achieved post-junctionally by ATP and NA acting via EJP-spike and spike-independent mechanisms, respectively. 2) If the two substances are stored in separate vesicle types (for example ACh or NA with some peptides), then differential release is possible at different impulse frequencies; the peptides released at higher frequencies modulate the role of the classical transmitter, by both prejunctional enhancement of its release and post-junctional facilitation of its action.     

Regional changes of the cholinergic system in the guinea-pig's brain after physostigmine

Riassunto L'eserina 0.2–5 mg/kg aumenta la ACh totale del cervello di cavia soprattutto nel telencefalo. Dopo trattamento sub-acuto, l'attività colinoacetilasica aumenta, forse per stimolazione mediata dei neuroni colinergici.