Actions of Some Anticholinesterases on the Smooth Muscle of the Chick Amnion

241

1Potential changes in rat superior cervical ganglia were recorded in vitro with surface electrodes.2 y-aminobutyric acid (GABA) produced a transient, low-amplitude ganglion depolarization at rest, and a transient hyperpolarization in ganglia depolarized by carbachol. Depolarization was not prevented by preganglionic denervation. The log dose-response curve for depolarization was sigmoid with a mean ED50 of 12.5 ,iM.3 The ganglion was depolarized in similar manner by the following compounds (mean molar potencies relative to GABA (= 1) in brackets): 3-aminopropane sulphonic acid (3.4), 'y-amino-f3-hydroxybutyric acid (0.27), ,B-guanidino-propionic acid (0.12), guanidinoacetic acid (0.057), 6-aminovaleric acid (0.048),,-alanine (0.01), 2,4-diaminobutyric acid, 'y-guanidinobutyric acid, taurine and N-methyl-GABA (all <0.01). The folfowing compounds did not depolarize the ganglion at 10 mM concentrations: ai-and ,B-amino-n-butyric acids, a-amino-isobutyric acid, glycine and glutamic acid. 4 Depolarization declined in the continued presence of GABA. Ganglia thus 'desensitized' to GABA showed a diminished response to other amino acids but not to carbachol. 5 The effect of GABA was not antagonized by hyoscine and hexamethonium in combination, in concentrations sufficient to block responses to carbachol. 6 Responses to GABA were blocked more readily than those to carbachol by bicuculline (IC50, 14 gM) and picrotoxin (IC50, 37 gM). Strychnine (IC50, 73 ,M) was a relatively weak and less selective GABA-antagonist. 7 It is concluded that sympathetic ganglion cells possess receptors for GABA and related amino acids which are (a) different from the acetylcholine receptors and (b) similar to GABA receptors in the central nervous system.

Section: (D) Significancementioning

confidence: 99%

DEPOLARIZING ACTIONS OF γ‐AMINOBUTYRIC ACID AND RELATED COMPOUNDS ON RAT SUPERIOR CERVICAL GANGLIA IN VITRO

Bowery

Brown

1974

241

“…Other suggested modes of action include a direct muscarinic action in the ileum (Harry, 1962) and a non-muscarinic intracellular site in chick amnion (Cuthbert, 1962) and toad bladder (Bell & Burnstock, 1965). By pharmacological depletion or inactivation of the cholinergic nerve endings it might be possible to decide the additional site of action of these anticholinesterases.…”

mentioning

confidence: 99%

pP₂ of eserine and neostigmine on acetylcholine responses of isolated ileum

Edge¹

1970

pP2 values of 7*9 and 8-0 for eserine and neostigmine show that these compounds are respectively about 200 and 300 times more potent in potentiating acetylcholine (ACh) responses on isolated cavy ileum than was previously found on frog rectus muscle. The increased tone and spontaneity usually produced by eserine and neostigmine were not prevented by morphine (10 to 100 ,ug/ml), which itself potentiated both ACh and histamine responses. Edge (1967) Results.- Figure 1 Fig. 1. were obtained in the presence of morphine, 10 jug/ml. However, morphine did not prevent spontaneity, tonal increase or mucus expulsion which occurred in three of the four ileal segments used (Fig. Id).Morphine alone also caused an increase in the response to a constant dose of ACh. This potentiation was slight with 10 Mg/ml but more marked with 100 ,ug/ml. These concentrations sometimes caused graded increases in rhythmic movements. The effects were quickly reversed following washout.The potentiating action of morphine was not ACh-specific. A similar potentiation of histamine responses (Paton, 1957) That anticholinesterases increase spontaneity and tone in various smooth muscle preparations is well known. Burn (1952) showed the effect in rabbit duodenum is glucose dependent. Paton (1957) found that morphine reduced the resting release from cholinergic nerve endings in cavy ileum and "quietened" the preparation. In the present experiments morphine tended to increase spontaneity. Carlyle (1963) attributed increase in tone of cavy trachealis muscle to stimulation of ACh release from nerve endings, an action of

“…Histologically it consists of a single layer of epithelial cells derived from ectoderm and a layer of smooth muscle derived from mesoderm (Romanoff, 1952). The muscle cells contain muscarinic acetylcholine receptors (Cuthbert, 1962a(Cuthbert, , 1963(Cuthbert, , 1964Evans & Schild, 1959) but more importantly it is never innervated, so that there is no possibility of binding to nervous elements. The amnion is only 20-30 ,um in thickness and hence diffusive delays are unlikely to create problems during labelling experiments.…”

Section: Introductionmentioning

confidence: 99%

The number of muscarinic receptors in chick amnion muscle

Cuthbert

Young

1973

Self Cite

Summary [3H]‐Propyl benzilylcholine mustard ([3H]‐PrBCM) an irreversible specific antagonist of muscarinic acetylcholine receptors, has been used to label the muscarinic receptors in the aneuronal muscle of isolated 11 day amniotic membranes of chick embryos. This muscle was found to have about 9 fmol/mg dry weight of receptor material. This is only 1–2% of the amount found in intestinal muscle. Pharmacological studies with isolated amniotic membranes using PrBCM show that labelling is to functional receptors and that the receptor reserve is small. The significance of the difference in receptor reserve in innervated and aneuronal plain muscle is discussed.