Systemic Effects of Adenosine Triphosphate

Abstract

The experiments described in the present paper were the outcome of an incidental observation made in decerebrate cats when adenosine triphosphate (ATP) was injected into the artery supplying a leg muscle, the tibialis anticus. These injections were intended to produce the direct muscle contracting action of ATP first described by Buchthal and Kahlson (1944). We started with small doses of ATP which gave no contractile response; the dose was then increased with the result that sometimes, but by no means always, immediate weak contractions could be recorded from the tibialis anticus, but the injections produced additional and more striking effects. After a latency of some 30 seconds, the time necessary for the ATP to reach the general circulation after having passed through the tibialis anticus muscle, respiratory changes occurred, followed by strong contractions of the skeletal muscles of the limbs and the whole body of the animal. ATP is known to produce profound changes in the cardio-vascular system (Drury and Szent-Gyorgyi, 1929;Gaddum and Holtz, 1933;Gillespie-, 1934;McDowall, 1944;Bielschowsky, Green and Stoner, 1946) and the possibility was therefore envisaged that these general effects might be the outcome of circulatory events.The present paper deals with circulatory, respiratory, and other systemic effects of ATP when injected into different parts-of the circulatory system. cannulated in this case. The heart rate was read from the tracing of the systemic blood pressure; for this purpose the drum was run at a fast speed. METHODSFor intravenous injections of ATP cannulae were tied into a jugular or femoral vein. When the ATP was intended to reach the systemic, without first passing the pulmonary circulation, it was injected either into the left auricle or through a glass cannula tied into the left auricle or through a long fine syringe needle, with a blunt tip, which was passed through an opening in the right external carotid or subclavian artery down to the base of the ascending aorta. Heparin was often given in these experiments. For injecting ATP into the brain circulation it was injected into the vertebral or external carotid artery. For the injections into the vertebral artery again a fine blunt needle attached to a syringe, filled with the amount of ATP to be injected, was passed through an arterial side branch into the vertebral artery. In order to ensure that all the injected ATP passed down the vertebral artery the vessel was sometimes tied over the needle during the injection, but immediately afterwards the ligature was loosened and the needle withdrawn so that the blood supply to the vertebral artery was restored. When ATP was injected into the external carotid, the carotid sinus region was usually denervated and the injections were made through a cannula tied into the lingual artery pointing toward the carotid, which during the injections was kept clamped at its aortic end with an arterial clip.When we began injecting A1T into the left coronary artery we used cats and introduced a fine blunt sy...

The capillary dilator substances in dry powders of spinal roots; a possible role of adenosine triphosphate in chemical transmission from nerve endings

“…Arterial injection of small amounts into the cervical region of the cat's spinal cord produces movements of the forelimbs which are thought to be due to direct stimulation of the ventral horn cells (Buchthal, Engbaek, Sten-Knudsen & Thomasen, 1947). Emmelin & Feldberg (1948) also found that ATP injected into the vertebral artery stimulated the medulla. Stimulating and depressing effects of ATP in the central nervous system have also been observed by Babskil & Malkiman (1950), Feldberg & Sherwood (1954 and G6pfert & P. Holton (unpublished).…”

The Pharmacology of Tryptamine

“…Respiratory aud cardiac effects in the cat are known to arise reflexly from vagal stimulation by a number of other substances includiiii: A.T.P. (Emmelin aud Feldberg, 1948), a toxic protein iu serum (Bnidio, 1900) and veratrine (Dawes, 1947).…”

Cardiovascular effects of hypotension induced by adenosine triphosphate and sodium nitroprusside on dogs with denervated hearts.

“…Heart rate Emmelin and Feldberg (1948) speculated that the bradycardia in the canine heart produced by ATP results mainly from stimulation of afferent vagal fibers. On the other hand, James (1965) observed sinus bradycardia in dogs from direct perfusion of the sinus node with ATP.…”