duration transmitter agents, or as long-range, long-duration circulatory 

 hormones. The short-range transmitters can be called neurohumors, and the more 

 characteristic hormones neurosecretory substances. Mollusks have 

 neurosecretory systems comparable with those of arthropods and vertebrates, 

 but less is known about their physiological roles. Isolated Venus heart can 

 be inhibited by direct electrical stimulation and it recovers soon after the 

 stimulus is stopped. Duration of inhibition is greatly prolonged after heart 

 is treated with an anti-cholinesterase like eserine. Inhibition is quickly 

 abolished when heart is bathed by an appropriate acetylcholine (ACh) antagonist 

 like tetraethylammonium. Mytolon is even more effective. When ACh reacts with 

 acceptor substance in V. mercenaria heart the cationic head of the ACh molecule 

 is important. Compounds with carbonyl group in the same relative position to 

 that in ACh are the most active. Sometimes Venus heart is excited after 

 inhibition produced by electrical stimulation of visceral ganglion. After an 

 ACh-blocking agent (Mytolon) was applied to heart, only excitation was seen. 

 Synthetic 5-HT excited Venus heart in low concentrations in a way that 

 parallelled closely that produced by nerve stimulation after ACh blockade. It 

 was important to know if 5-HT was present in the molluscan nervous system. 

 Venus ganglia by chance turned out to be highly favorable material, and it was 

 shown by various methods that 5-HT is present in Venus and other molluscan 

 nervous systems. LSD, a derivative of lysergic acid, in trace amounts, excited 

 Venus heart in a way similar to that produced by 5-HT. As little as 10~16 M 

 LSD will produce a maximal increase in amplitude of beat, which is only 

 partially reversed after prolonged washing. Some closely related lysergic acid 

 derivatives have little or no exciter action but instead are effective 5-HT 

 antagonists. This important review paper describes the status, at time of 

 publication, of work in the U.S. and Europe on molluscan neurohormones. 

 - J.L.M. 



1976 



Welsh, John H. 1968. 



Distribution of serotonin in the nervous system of various animal species. 

 Adv. Pharmacol. 6A(Pt.2): 171-188. 



Serotonin has a strange distribution in nature. In plants it occurs in fruits 

 such as bananas and the urticant fluid of stinging nettle. In animals it is 

 present in unusually high concentrations in venoms of social wasps, some 

 spiders and scorpions, and terrestrial and semi terrestrial toads and frogs. 

 It is found in enterochromaf f in cells of the intestine in all vertebrate classes 

 and in blood platelets and mast cells of mammals. Presence of 5-HT (5- 

 hydroxytryptamine, serotonin) in nervous systems was unsuspected until the 

 early 1950s. 5-HT-containing neurons in vertebrates and invertebrates can be 

 recognized by their characteristic yellow fluorescence after f reeze-drying and 

 reacting with formaldehyde vapor, and can be distinguished from green- 

 fluorescing catecholamine-containing neurons. Ganglia of bivalve mollusks 

 contain the highest levels of 5-HT found so far in any nervous system. It was 

 fortunate coincidence that the first attempt to isolate 5-HT from an 

 invertebrate system used ganglia from Mercenaria (Venus) meraenaria. Molluscan 

 ganglia contain enzymes required for synthesis of 5-HT. The 5-HT is stored in 

 membrane-bound vesicles. Many drugs that act on the 5-HT system in mammals 

 have similar action on mollusks. For example, D-lysergic acid diethylamide 

 mimics action of 5-HT on Mercenaria heart; methysergide is a highly effective 

 blocking agent; and reserpine releases 5-HT. 5-HT has been found in many 

 other invertebrates, from protozoa to echinoderms and protochordates . - J.L.M. 



1977 



Welsh, John H. 1971. 



Neurohumoral regulation and the pharmacology of a molluscan heart. Comp. 

 Gen. Pharmacol. 2(8): 42 3-4 32. 



This most interesting paper reviews some major developments during 30 years 

 of research on neurohumoral regulation of heart of Mercenaria . (Venus) 

 meraenaria. It should be read as an introduction to the relatively voluminous 

 literature on the subject, including research on other mollusks. The intent 

 was to show how complex the regulation of the heart of a relatively primitive 

 animal can be, and also to point out how studies on such a heart may reveal 

 new facts and principles that have application elsewhere. Among these were: 



550 



