not possible to stimulate beating of Mercenaria hearts made hypodynamic by 

 cooling and keeping clams dry in a refrigerator for a week. Only the 

 depressor response of the heart to ACh is well established as mimicking a 

 physiological role of endogenous neurohumor. (Abstracter's note: This is 

 primarily a comparative review paper, although it does contain some original 

 data. Out of context, the references to M. mercenaria are somewhat 

 disjointedj - J.L.M. 



703 



Greenberg, M. J. 1966. 



Species specific effect of acetylcholine on bivalve rectums. Science 154 

 (3752) : 1015-1017. 



Experiments on 2 species of Katelysia showed that the pharmacology of rectums 

 was very different. Discernible differences in pharmacology of Mercenaria 

 mercenaria and M. campechiensis were not observed. - J.L.M. 



704 



Greenberg, Michael J. 196 9. 



The role of isoreceptors in the neurohormonal regulation of bivalve hearts. 

 In Comparative Physiology of the Heart: Current Trends. F. V. McCann (edj 

 Experientia Supplementum 15. Birkhauser Verlag, Basel: 250-265. 



A generalized outline of pharmacology of 4 presumed neurotransmitter 

 substances on hearts of bivalve mollusks has emerged from research over 

 about 25 years. Most of the conceptual outline was developed in the 

 laboratory of John H. Welsh on heart of Mercenaria (Venus) mercenaria. 

 Acetylcholine (ACh) has been shown to be a depressor neurohumor. Curare-like 

 drugs are the most effective ACh-blocking agents. 5-Hydroxytryptamine (5HT 

 or serotonin) is an excitor transmittant. Lysergic acid diethylamide (LSD) 

 mimics the action of 5HT on many molluscan muscle preparations. On hard clam 

 heart the maximally effective dose is incredibly low. Effective blocking 

 agents for 5HT and LSD are 2-bromo-d-lysergic acid diethylamide (BOL) and 

 methysergide (UML) . Effects of catecholamines, such as epinephrine and 

 norepinephrine, are varied and depend on animal and dose. Usually tone and 

 frequency are increased. No effective antagonist to action of any 

 catecholamine has been found. Dopamine, and more rarely other catecholamines, 

 have been found in ganglia and some other bivalve tissues, but a 

 physiological role of dopamine in regulation of bivalve hearts was not 

 considered likely. A group of cardio-active substances, which may be 

 polypeptides, have been extracted from clam ganglia and hearts. They are 

 called collectively Substance X. These may play a role in starting, and 

 long-term maintenance of, cardiac rhythmicity in bivalves and other mollusks. 

 Study of drug actions on other species, many unrelated to Mercenaria , has 

 brought out a number of exceptions to this theoretical pharmacological 

 outline. Most of these responses have been markedly different from those of 

 M. mercenaria. The various mechanical responses of bivalve hearts to 

 neuromuscular drugs seem to have arisen independently many times during the 

 history of the Class. Once having appeared, however, they are sufficiently 

 stable so that knowledge of the Family of a particular species often allows 

 prediction of how its heart will react to pharmacological agents. Bivalve 

 hearts as a group are a tool for attack on the general problem of species 

 variability in chemical transmission and the pharmacology associated with 

 this process. Wide occurrence of ACh, 5HT, and catecholamines (mainly 

 dopamine) in nervous systems of bivalves is well established. Components of 

 Substance X may also have universal distribution. Enzymes involved in 

 synthesis and oxidation of 5HT have been identified in various molluscan 

 tissues, as has acetylcholinesterase. Species differences in 



acetylcholinesterase activity in hearts of oysters and hard clams can account 

 for observed differences in responses of these organs to ACh. Receptors are 

 identified by challenging the heart with a series of ketoamyltrimethylammonium 

 ions. Depressor receptors respond optimally to 4-ketoamyltrimethylammonium. 

 Mercenaria and oyster hearts have only this type of receptor. Tresus and 

 Spisula also respond optimally to the 3-keto compound, and have excitor as 

 well as depressor receptors. Upon adsorption of the neurohumor to its 

 receptor, the resulting complex, perhaps by changing the molecular 



197 



