EFFECTS ON TISSUE FUNCTIONS 949 



mercurials in vivo can produce intestinal stimulation by such a selective 

 inhibition, and the subject needs further investigation. 



Another mechanism which must be given serious consideration is hista- 

 mine release. Bachmann (1938) showed that the isolated cat intestine ex- 

 posed to Hg++ releases a substance which behaves like histamine pharma- 

 cologically, and felt that at least some of the action on the intestine can be 

 explained by this release. It may be mentioned that Hg++ has been report- 

 ed to release histamine from perfused dog Kver (Feldberg and Kellaway, 

 1938) and p-MB to release histamine from rat mast cells (Bray and Van- 

 Arsdel, 1961), but in both cases the concentrations used were too high to 

 enable correlation with in vivo effects; it is quite likely that any substance 

 at high enough concentration or any irritant histotoxic agent will release 

 histamine. 



Nervous System 



Neurological dysfunction is common in mercury poisoning (page 951 ) but 

 it is not known if the action is axonal or synaptic. One usually assumes that 

 metabolic disturbances affect primarily junctional transmission. Halasz et 

 al. (1960) have shown that transmission in the cat superior cervical gan- 

 glion is rapidly and reversibly depressed by p-MB at 0.0056-0.02 mM, while 

 simultaneously the effects of injected acetylcholine are potentiated. If the 

 concentration is increased toward 0.028 mM, this potentiation of acetyl- 

 choline is lost. The stimulatory action of K+ is unaffected by lower and 

 depressed by higher concentrations. Inhibition of acetylcholine synthesis is 

 apparently not involved since there is a store of acetylcholine and the de- 

 pression of transmission is immediate, so the authors postulate a reduction 

 of the response of the postganglionic cells to acetylcholine. However, at the 

 time of the initial suppression of transmission there is actually a potentia- 

 tion of the acetylcholine response, which is difficult to explain, particularly 

 since cholinesterase inhibition is not a likely hypothesis for ganglia. It is 

 possible that SH groups of the acetylcholine receptors are reacted at higher 

 concentrations of the mercurial, as has been suggested for cardiac receptors. 

 Recordings of the postganglionic membrane potential changes are needed 

 to interpret these results. 



Axonal conduction is also depressed by p-MB at low concentrations (H. 

 M. Smith, 1958). Conduction in the frog sciatic nerve is blocked in 4 min 

 by 0.002-0.02 mM p-MB and in lobster giant axon in 3 min by 0.045-0.07 

 mM p-MB. There is a gradual depolarization of the axon but block occurs 

 long before the potential is lost. The post-tetanic hyperpolarization of sym- 

 pathetic C fibers is more sensitive to metabolic inhibitors than the magnitude 

 of the action potential, and is decreased by mersalyl at 0.34 mM (Greengard 

 and Straub, 1962). However, the nature of such a hyperpolarization and its 

 significance for conduction are not understood. The injection into the squid 

 axon of 6 X 10~^ ml/mm of 7.5 mM p-MB is without effect on the action 



