Depressing Effect of Caffeine at Crayfish Neuromuscular Synapses II. Initial Search for Possible Sites of Action

Abstract

Caffeine's unexpected depression of synaptic transmission in the superficial flexor muscle system (SFM) of Procambarus clarkii was studied by looking at three known sites of action of this drug: via adenosine and ryanodine receptors and inhibition of phosphodiesterase.1. JPs did not change in size when exposed to physiological concentrations of adenosine, suggesting that the SFM system lacks presynaptic adenosine receptors.2. JPs slightly increased in size in the presence of a phosphodiesterase inhibitor, the opposite response to that obtained with caffeine, suggesting that caffeine is not acting via this pathway.3. A calcium ionophore immediately enhanced synaptic transmission in the SFM system but when given in combination with caffeine the enhancement is reduced and declines over time.4. Serotonin enhanced synaptic transmission in the SFM system, but when given in combination with caffeine this enhancement was not observed.5. These caffeine effects are interpreted in terms of alterations to the calcium homeostatic mechanisms of the terminals.

Evolutionary origins of the purinergic signalling system

“…2006). In contrast to vertebrate neuromuscular junctions, caffeine had a depressant action at neuromuscular synapses in the crayfish Procambarus clarkii , perhaps indicating an excitatory effect mediated by pre‐synaptic adenosine receptors (Celenza et al. 2007).…”

Depressing Effects of Caffeine at Crayfish Neuromuscular Synapses I. Dosage Response and Ca++ Gradient Effects

“…Attempting to unmask the myriad pathways and molecular interactions regulating calcium homeostasis in synaptic terminals (Thayer et al, 1988;Tsien, 1990;Miller, 1991;McBurney and Neering, 1997) to understand the particular caffeine effect detected in the SFM system is a very long multi-step process beyond the original scope of this work. Caffeine's multiple sites of action (Snyder and Sklar, 1984;Nehlig et al, 1992;Fredholm et al, 1999) warrant an exhaustive follow-up, one that we begin in the following paper with the techniques at our disposal (Celenza et al, 2006). Choosing caffeine as our first drug to categorize the physiological properties of these terminals in control animals in order to study their emergence during regeneration of connections, and observing its unexpected depressing effect on synaptic transmission, pauses our regeneration work until this unexpected caffeine response is further analyzed.…”

“…As will be shown in this work, the results obtained were a decline and eventual inhibition of transmitter release in the presence of caffeine, opposite of what we expected. Whether this is a new effect of caffeine, whose multiple effects probably have not all being accounted for, or can be explained using caffeine's known sites of action, is addressed in the companion paper (Celenza et al, 2006). In trying to obtain a pharmacological marker that could be used to label original, regenerated and transplanted contacts, we have stumbled on a very interesting novel effect of one of the most widely used drug in the world today, and this warrants our attention.…”

Modulatory Roles of ATP and Adenosine in Cholinergic Neuromuscular Transmission

“…In recent years, there has been an expansion in the field of studies of the modulating effects of purines in neuromuscular junctions [64][65][66][67][68][69][70][71][72][73][74][75][76][77][78][79]. Along with studies on the refinement of the subtype of the presynaptic P2 receptor involved in modulation in "classical" preparations [64,65,69,70,[73][74][75]77,78], studies are being conducted to cover a broader spectrum of types of motor units in different laboratory animals [67,68,71,72,76,79] (see Table 1). Notes: The arrows indicate the direction of the effect: ↑-facilitation; ↓-inhibition.…”