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.     

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.     

A marine mollusc provides the first example of in vivo storage of prostaglandins: prostaglandin-1,15-lactones

Prostaglandin-(PG) 1,15-lactones and, in smaller amounts, free acids, were isolated from both the mantle and the dorso-lateral appendices of the opisthobranch mollusc Tethys fimbria. In vivo conversion of PGs into the corresponding lactones and accumulation of PGE2- and PGE3-1,15-lactones in the appendages were shown. The detachment of these appendages from the molested mollusc caused the in vivo conversion of PGE2- and PGE3-lactones back to PGE2 and PGE3 respectively, thus providing the first example of a mechanism by which prostaglandins can be stored and, when needed, released.     

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.     

Impulsantworten des Nervus opticus auf Reizung der Netzhaut mit Acetylcholin

Summary Application of ACh on the isolated perfused retina of the frog elicited spikes of the optic nerve. The extent of this spike activity depended on the amount of ACh applied. The retinal response to ACh was varied by prostigmine and atropine as expected by their pharmacological properties. From these experiments it cannot be concluded that ACh is acting on the synapses of the firing ganglion cells directly.     

Opposite effect of PGE2 on cAMP levels in human adrenal medulla and pheochromocytoma.

PGE2 (10(-7) M) caused increased cAMP accumlation in 5 pheochromocytomas, while in 3 human adrenal medullae PGE2 caused a significant decrease of cAMP level on incubating slices in vitro. This finding is discussed in relation to the opposite effect of PGE2 on catecholamine release from human medulla and pheochromocytoma slices in vitro.     

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.     

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

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.     

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.     

Serum and bile modifications in the guinea-pig following chronic treatment with PGE1 and PGE2.

PGE1 increases cholesterolemia without lipemia modifications. In bile there are not modifications in cholesterol levels and total lipids appear diminished. PGE2 raise the lipemia and have no effect in cholesterolemia, moreover bile cholesterol and total lipids exhibit no changes. Both PGE1 and PGE2 decreased the bile volume.     

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.     

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.     

A tissue-selective prostaglandin E2 analog with potent antifertility effects.

N-methanesulfonyl 16-phenoxy-omega-tetranor PGE2 is a prostaglandin analog which is markedly more tissue selective than PGE2. This compound is 10-30 times more potent than PGE2 in animal models which are considered relevant to antifertility effects in humans. In pharmacological tests which are believed to be predictive for side effects in humans, the compound has potency either equal to or less than that of PGE2.     

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.     

Tricyclic antidepressants antagonize prostaglandin (PG) E2-induced contractions of the guinea pig ileum and hypomotility in the mouse

The interactions of PGE2 and 2 tricyclic antidepressants were tested both on the guinea pig ileum and motility in the mouse. PGE2-induced contractions of the guinea pig ileum were irreversibly blocked by amitriptyline and desipramine. Chronic administration of amitriptyline and desipramine blocked PGE2-induced hypomotility in the mouse.     

ACTH response induced by interleukin-1 is mediated by CRF secretion stimulated by hypothalamic PGE

We investigated whether hypothalamic prostaglandin E2 (PGE2) and corticotropin releasing factor (CRF) are responsible for the development of the adrenocorticotropic hormone (ACTH) response induced by interleukin-1 alpha (IL-1 alpha). The present results show that ACTH responses induced by intravenous injection of IL-1 alpha were suppressed by systemic pretreatment with indomethacin and that intrahypothalamic injection of PGE2 stimulates the secretion of ACTH. Furthermore, systemic pretreatment with anti-CRF antibody significantly suppressed the ACTH response induced by intrahypothalamic injection of PGE2. These data suggest that the ACTH response induced by IL-1 is mediated by CRF secretion stimulated by hypothalamic PGE2.     

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.     

Role of 5-hydroxytryptamine in prostaglandin E1-induced potentiation of hexobarbitone hypnosis in albino rats.

PGE1 potentiated, while diclofenac, a prostaglandin synthesis inhibitor, antagonized hexobarbitone hypnosis in rats. PGE1-induced potentiation of hexobarbitone sleep was inhibited by a 5HT synthesis inhibitor and by a 5HT receptor blocker, suggesting that this potentiation is 5HT mediated.     

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.