Internal calcium stores and norepinephrine overflow from isolated, field stimulated rat vas deferens.
Ryanodine has been shown to selectively inhibit the initial phase of contraction of rat vas deferens smooth muscle stimulated by endogenous release of norepinephrine (NE) (1), and part of this effect could be pre-junctional. To assess this, its effect on NE overflow was measured in the same preparation. NE overflow from electrical field-stimulated isolated rat vas deferens was quantified by electrochemical detection using HPLC. In order to limit pre-junctional autoregulatory mechanisms, alpha2-adrenergic receptors were blocked and P2x purinergic receptors were desensitized. In these experimental conditions, NE overflow was directly proportional to extracellular Ca2+ concentration. Ryanodine only induced a modest decrease in NE overflow. Cyclopiazonic acid (CPA), an inhibitor of sarcoplasmic reticulum Ca2+-ATPase, slightly increased NE overflow but decreased smooth muscle contraction induced by electrical field stimulation. It is concluded that part of the effect of ryanodine on field stimulation-induced contraction may be due to an inhibition of NE release, although the major inhibitory effect of this alkaloid is post-junction. For CPA, its inhibitory effect on field stimulation-induced contraction is entirely post-junctional. Its effect on NE overflow suggests that, in this preparation, internal Ca2+ stores could function to accelerate termination of neurotransmitter release by sequestering cytosolic Ca2+.
Bourreau
J P
JP
Department of Physiology, Faculty of Medicine, University of Hong Kong.
D000818:Animals; D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors; D002851:Chromatography, High Pressure Liquid; D003600:Cytosol / Q000378:metabolism; D004558:Electric Stimulation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology; D009638:Norepinephrine / Q000032:analysis / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012433:Ryanodine / Q000494:pharmacology; D012519:Sarcoplasmic Reticulum / Q000201:enzymology; D014649:Vas Deferens / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*
D004791:Enzyme Inhibitors; D012433:Ryanodine; D000252:Calcium-Transporting ATPases; D002118:Calcium; D009638:Norepinephrine