Differential cotransmission in sympathetic nerves: role of frequency of stimulation and prejunctional autoreceptors.
Recent reports have suggested that sympathetic nerves may store separately and release independently the cotransmitters ATP and norepinephrine (NE). It is conceivable therefore that the quantity of each neurotransmitter that is released from the nerves is not fixed but rather may vary, possibly with the frequency of stimulation. To test this hypothesis we studied the concomitant release at various frequencies and cooperative postjunctional actions of ATP and NE during the first 10 s of electrical field stimulation of the guinea pig vas deferens. We found that at lower frequencies (8 Hz), prejunctional inhibition of the release of NE, which occurs via alpha2-adrenoceptors, modulates the ultimate composition of the cocktail of cotransmitters by limiting the amount of NE that is coreleased with ATP. As the frequency of stimulation increases (above 8 Hz), the autoinhibition of the release of NE is overridden and the amount of NE relative to ATP increases. The smooth muscle of the guinea pig vas deferens reacts to changes in composition of the sympathetic neurochemical messages by increasing the amplitude of its contractions due to the enhancement by NE of the contractile responses triggered by ATP. This evidence suggests that the prejunctional alpha2-adrenoceptor may function as a sensor that "reads" the frequency of action potentials produced during a burst of neuronal activity and converts that information into discrete neurochemical messages with varying proportions of cotransmitters. The mechanism for decoding the informational content of these messages is based on the cooperative postjunctional interactions of the participating cotransmitters.
Todorov
L D
LD
Department of Pharmacology, University of Nevada School of Medicine, Reno, Nevada, USA. todorov@med.unr.edu
Mihaylova-Todorova
S T
ST
Bjur
R A
RA
Westfall
D P
DP
D000255:Adenosine Triphosphate / Q000502:physiology*; D058647:Adrenergic alpha-2 Receptor Agonists; D058669:Adrenergic alpha-2 Receptor Antagonists; D000818:Animals; D017660:Autoreceptors / Q000187:drug effects / Q000502:physiology*; D004558:Electric Stimulation; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000502:physiology; D009130:Muscle, Smooth / Q000294:innervation / Q000502:physiology; D009469:Neuromuscular Junction / Q000187:drug effects / Q000502:physiology; D009638:Norepinephrine / Q000502:physiology*; D018341:Receptors, Adrenergic, alpha-2 / Q000502:physiology; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*; D014649:Vas Deferens / Q000294:innervation / Q000502:physiology
D058647:Adrenergic alpha-2 Receptor Agonists; D058669:Adrenergic alpha-2 Receptor Antagonists; D017660:Autoreceptors; D018341:Receptors, Adrenergic, alpha-2; D000255:Adenosine Triphosphate; D009638:Norepinephrine