The release of chemical transmitter from the sympathetic nerves of the intestine of the cat

Abstract

In a previous paper (Brown & Gillespie, 1957) we have shown that the noradrenaline released when the sympathetic nerve supply to the spleen is stimulated can be estimated in the venous blood leaving the organ. The maximum output per stimulus occurred at frequencies of 30/sec. Administration to the animal of substances blocking the effect of the liberated transmitter on the innervated cells increased the output of noradrenaline at frequencies below 30/sec.These experiments were made on the spleen of the cat because it was the only tissue from which we could regularly obtain amounts of transmitter sufficient for an adequate assay. From the colon of the cat and the ear of the rabbit, for instance, we could obtain either no transmitter at all or amounts at the lower limit of detectability. The spleen, however, has certain disadvantages as a tissue for these experiments; the circulation of blood through it is complex and obscure, stimulation of the nerves causes an expulsion of stored red cells, and this effect is absent after a blocking agent has been administered. All these factors might influence the appearance of liberated transmitter in a venous sample, without necessarily reflecting changes in the amount liberated or destroyed in the vicinity of the nerve endings.We have accordingly re-investigated the intestines in the light of the information we obtained from the spleen. The administration of a sympathetic blocking agent has again been found to increase the amounts of transmitter detectable in the venous blood. Three substances to which anti-amine oxidase activity has been attributed were found to be without effect on the output of transmitter. Additional information has been obtained about the factors governing the release and appearance of the sympathetic transmitter.

Correlation between the response of the heart to sympathetic stimulation and the release of endogenous catecholamines into the coronary sinus of the dog.

“…Most previous experiments in which norepinephrine overflow in response to nerve stimulation has been studied were carried out using stimulation frequencies ranging from 10 to 50 Hz or more (16)(17)(18)(19)(20)(21)(22)(23). In these experiments carried out on isolated, perfused organs, the amount of norepinephrine released into the venous effluent or perfusate was determined mainly by bioassay techniques (16)(17)(18)(19), spectrofluorometric measurements (22), or through the use of labeled norepinephrine (20,21,23).…”

“…In these experiments carried out on isolated, perfused organs, the amount of norepinephrine released into the venous effluent or perfusate was determined mainly by bioassay techniques (16)(17)(18)(19), spectrofluorometric measurements (22), or through the use of labeled norepinephrine (20,21,23). Mainly because previous techniques have lacked the sensitivity needed to detect small changes in the levels of endogenous catecholamines in the plasma, it has been impossible to accurately measure the effects of low-frequency stimulation on the order of 1-3 Hz and correlate them with physiological responses under basal conditions so far in vivo.…”

The Effect of Phenoxybenzamine and of Tolazoline on the Response to Sympathetic Stimulation

“…In a series of papers (Brown & Gillespie, 1957;Brown, Davies & Gillespie, 1958;Brown, Davies & Ferry, 1961;Blakeley, Brown & Ferry, 1963) experiments have been described in which the postganglionic sympathetic fibres have been stimulated to an organ (mostly the spleen) in the cat and the amount of noradrenaline has been measured in the blood in the vein leaving the organ. The effect of antiadrenaline substances, in particular phenoxybenzamine and Hydergine (which may be described as dihydroergotoxine methanesulphonate), was determined, and it was observed that in their presence the output of noradrenaline was greatly increased when stimulation was applied at 10 shocks/ sec, though at a higher frequency the increase in the output was much less.…”

The Effect of Reserpine on the Pressor Response to Injection of 2‐halogenoethylamine

“…These results suggest a direct release of pressor amines from the adrenal medulla while nervous influence is reduced by the ganglion blocker. Brown & Gillespie (1957) and Brown, Davies & Gillespie (1958) have shown that administration of phenoxybenzamine causes a greater release of amine from a tissue when the sympathetic nerve supply is stimulated than takes place without the influence of this 2-halogenoethylamine, while Schapiro (1958) demonstrated an increased urinary excretion of noradrenaline and a loss of catechol amines from the heart, adrenals and spleen after giving this compound.…”