Both Paton (1957) and Schaumann (1957) have shown that morphine inhibits the release of acetylcholine from the isolated guinea-pig ileum suspended in eserinized physiological salt solution. The resting output of acetylcholine as well as the output during stimulation of the nerve endings in the intestinal wall is reduced when morphine is present in the bath fluid. According to these authors the inhibition of acetylcholine release is responsible for the paralysing action of morphine on the guinea-pig intestine. The present experiments were designed to find out whether morphine similarly depresses the release of acetylcholine from the central nervous system.When the cerebral ventricles of the cat are perfused with physiological salt solution containing an anticholinesterase acetylcholine appears in the effluent and it has recently been shown (Beleslin, Carmichael & Feldberg, 1964) that the greatest amount originates from structures lining the anterior horns of the lateral ventricles. In the present experiments therefore the method of perfusing the anterior horn of a lateral ventricle with an anticholinesterase was used to study the effect of morphine on the output of acetylcholine. In a similar way, the effect of chloralose was examined. METHODSCats of both sexes weighing between 1-8 and 3-6 kg were anaesthetized with chloralose (40-70 mg/kg) injected into the cannulated right femoral vein. To allow cannulation of the femoral vein, anaesthesia was induced with ethyl chloride and ether. The trachea was cannulated. With the cat lying on its belly the head was fixed to the ear bars and the mouthpiece of a head holder similar to that of a Horsley-Clark stereotaxic instrument. The surface of the skull was widely exposed and the muscles covering the atlanto-occipital membrane were dissected away.The anterior horn of the left lateral ventricle was perfused with neostigmine methyl sulphate in a concentration of 1/50,000. The method used was that of multiple cannulation of the ventricular system which is based on the principle that drugs perfused through one part of the ventricular system are denied access to those parts which are cannulated and perfused with artificial c.s.f. t NATO Science Fellow.

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Blood samples were collected from anaesthetized cats during haemorrhage or stimulation of the peripheral end of the vagus. Vasopressin and oxytocin were estimated in the samples by assaying alcohol extracts for antidiuretic activity in the water loaded rat and for milk-ejecting activity in the lactating guinea-pig. Haemorrhage caused vasopressin to be released into the blood with out detectable amounts of oxytocin. A similar result was obtained with vagal stimulation provided that the fall of blood pressure which it produced exceeded a critical value of about 80 mmHg. Failure to detect oxytocin in blood samples containing vasopressin was not due to the presence of adrenaline or any other inhibitory substance in the extracts blocking the response of the mammary gland to oxytocin. The stimulus for the independent release of vasopressin by haemorrhage appears to be the associated fall in arterial blood pressure.

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The introduction of substance P into the lumen of the isolated guinea-pig ileum caused an increase in the number and amplitude of the peristaltic waves. In preparations in which the peristaltic reflex was abolished, by fatigue, by external or internal application of 5-hydroxytryptamine, or by lowering the temperature of the bath, the introduction of substance P into the lumen of the intestine restored peristalsis. This effect of substance P was absent in preparations in which the mucous membrane was removed. Hexamethonium abolished the effect of substance P on peristalsis. It is concluded that substance P acts on the afferent nervous elements of the peristaltic reflex arc, possibly on the sensory receptors.Substance P has been found in relatively high amounts in the intestine and brain of various animals, such as the monkey, horse, ox, pig, sheep, dog, cat, rabbit and man (v. Euler and Gaddum, 1931;Douglas, Feldberg, Paton and Schachter, 1951;Ehrenpreis and Pernow, 1952;Pernow, 1953). A factor having, qualitatively and quantitatively, the same properties as substance P has been shown to occur in the intestine of the cod and the dogfish and in cod brain (v. Euler and Ostlund, 1956). The retina of the cow has also been found to contain high amounts of substance P (Duner, v. Euler and Pernow, 1954).The exact physiological role of substance P is still unknown. A central stimulating effect of substance P has been shown by v. Euler and Pernow (1954), and evidence has been presented that substance P stimulates afferent fibres (Lembeck, 1957). In evaluating the action of substance P on the jejunum of the rabbit, Blair and Clark (1956) concluded that the stimulant action of substance P on intestinal motility is mediated through a very labile mechanism which could well have a trophic influence on the amplitude of spontaneous contractions. It is known that the peristalsis elicited by increased intraluminal pressure is augmented in the presence of substance P (Gernandt, 1942). In the present experiments the effect of substance P on the peristaltic reflex was studied, introducing the substance into the lumen of the guinea-pig ileum. MATERIALS AND METHODSFor recording the peristaltic activity a modification of the method of Trendelenburg (1917) was used, which has been described in detail in a previous paper (Beleslin and Varagid, 1958). By this method it was possible to introduce the drug into the lumen of the intestine and to wash it out. The peristaltic activity was recorded by means of Stephenson's float recorder which records volume changes (Stephenson, 1948).The peristaltic reflex was tested by raising the intraluminal pressure (varying from 30 to 50 mm. in different experiments) for 90 sec. at constant intervals.Several experiments were done with preparations from which the mucosa had been removed. For this purpose a loop of intestine was turned inside out by slipping it over a glass rod. The mucosa was gently scraped off using a piece of filter paper, and then the loop of intestine was returned to its normal position...

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