The vasodilator activity of spinal roots

Abstract

In 1935, Dale suggested that the identification of the chemical transmitter responsible for antidromic vasodilatation would be a useful approach to the problem of sensory transmission in the central nervous system since it is likely that the transmitter is the same at both ends of the sensory neurone. One of the difficulties in searching for the transmitter at central sensory endings is the lack of a specific pharmacological test for it. However, if the transmitter is also responsible for antidromic vasodilatation, it should be possible to detect it by its vasodilator activity in those organs in which antidromic vasodilatation can be elicited. This approach was used by Hellauer & Umrath (1947, 1948), who studied the effects of injecting extracts of dorsal and ventral roots into the rabbit's ear. As a result of their experiments they claim that: (1) dorsal roots contain a vasodilator substance which is neither acetylcholine nor histamine; this substance is absent from ventral roots; (2) sensory denervation increases the sensitivity of the rabbit's ear to the substance; (3) the vasodilator substance is enzymically destroyed when incubated for 20 hr, the enzyme activity being greatest in dorsal roots and less in ventral roots and preganglionic sympathetic fibres; (4) the enzyme is inhibited by strychnine.They conclude that the vasodilator substance is the transmitter liberated at sensory nerve endings.Since this claim is of far-reaching significance for the theory of central synaptic transmission we have repeated and extended their experiments and were able to confirm some, but not all, of their results. In our view, the eyidence now available is not sufficient to support the general conclusion of Hellauer & Umrath. METHODS Spinal root extract8Extracts were prepared from the spinal roots ofhorses which were dissected in the slaughter-house. The dissection was started about 25 min after the death of the animal and took 10 min for each horse. Starting at the last sacral segment, the ligamentum denticulatum was identified between * Beit Memorial Research Fellow.

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

“…These were carried out by the rabbit's ear method already described (Holton & Holton, 1952), using rabbits whose ears were denervated by section of the great auricular nerve and removal of the superior cervical ganglion at the beginning of the experiment. The vessels of the ear were made insensitive to acetylcholine and histamine by giving atropine (5mg/kg) and mepyramine (2-5 mg/kg) intravenously every 3 hr.…”

“…Acid or alkali were added to the extracts which were then held in a boiling water-bath for 20 min as described previously (Holton & Holton, 1952 (1952, fig. 5) Solvent-extracted spinal root powders the vasodilator substance in our extracts resembles ATP and differs from substance P in its relative stability to hot alkali.…”

Substance P: Its Pharmacology and Physiological Roles

“…The intravenous or intra-arterial injection of erude substanee P preparations caused a transient fall in blood pressure as a result of peripheral vasodilatation (Euler and Gaddum, 1931;Euler, 1936a;Holton and Holton, 1952;Pernow, 1953;Erspamer, 1961;Stiirmer and Franz, 1961;Zetler, 1963). This effect apphed to birds (Bunag and Walaszek, 1963) and all mammals, including man (Pernow, 1963) but there were eonsiderable differences in sensitivity between species.…”

“…Cross circulation experiments in the dog provided no evidence for a centrally mediated cardiovascular action for substance P (Kato and Buckley, 1965). Moreover, vasodilatation was elicited in the vasculature of the isolated chicken wing (Bunag and Walaszek, 1963) and the chronically denervated isolated perfused rabbit ear (Holton and Holton, 1952;Amin et al, 1954). In mammals, circulatory responses to substance P were not abolished by atropine, ganglion blocking agents, antihistaminic drugs and guanethidine (Pernow, 1953(Pernow, , 1961Beck, 1965;L6fstr5m, Pernow and Wahren, 1965).…”

The Kallikrein-Kinin System as a Regulator of Cardiovascular and Renal Function

“…The seminal finding was the demonstration by Holton & Holton, Kellet, and Lewis (109,125,132) that subcutaneous injections of bradykinin reproduce some of the cardinal signs of acute inflammation: vasodilatation (rubor and calor), increased vascular permeability (as evidenced by a protein-rich exudate, tumor, or infiltration of injured tissue by neutrophils) and pain. Furthermore, components of the KKS are also found in inflammatory exudates [for a review, see (97)].…”