Abstract
The purinergic response of the guinea-pig vas deferens to long trains of pulses at high frequency consists of an initial twitch followed by a much lower plateau. Mechanical, neurochemical and electrophysiological techniques were used to examine the reason for the fade.
Mechanical measurements. In tissues stimulated by trains of 180 pulses/10 Hz and treated with prazosin to suppress the noradrenergic contraction component, the response to α,β-methylene ATP and to exogenous ATP was as high during the secondary plateau of the purinergic neurogenic contraction as it was outside electrical stimulation periods; the response to 50 pulses/100 Hz was also unchanged during the low plateau. The plateau was not increased by reactive blue 2, 8-(p-sulphophenyl)theophylline, propranolol or capsaicin. Neurochemical measurements. In tissues preincubated with [3H]-noradrenaline, electrical stimulation elicited an overflow of tritium and of ATP. In the absence of drugs as well as in the presence of prazosin and suramin to suppress contractions, the overflow of tritium per pulse decreased slightly in the course of trains of 90 pulses/10 Hz; the overflow of ATP per pulse decreased to a greater extent on average, but the decrease was not statistically significant. In the presence of prazosin and nifedipine, also to suppress contractions, the overflow of tritium per pulse again decreased slightly in the course of trains of 105 pulses/10 Hz, but the overflow of ATP per pulse if anything tended to increase. Electrophysiological measurements. Extracellular recording in the presence of prazosin showed that electrical stimulation by 180 pulses/10 Hz elicited excitatory junction currents (EJCs) which facilitated and summated to reach threshold for the initiation of action potentials in the smooth muscle cells. In most tissues, smooth muscle action potentials ceased after a few seconds although EJCs continued. Intracellular recording in the presence of prazosin and nifedipine showed that excitatory junction potentials (EJPs) elicited by 180 pulses/10 Hz facilitated and summated to a plateau after about 10 stimuli. The EJPs continued unchanged, and the plateau depolarization was maintained, throughout the train.
It is concluded that the fade of the purinergic neurogenic contraction is not due to P2Y-purinoceptor desensitization. It also is not due to a secondary relaxation mediated by P2Y- or P1-purinoceptors, β-adrenoceptors or a compound originating from primary afferent axons. Moreover, a fade of the release of ATP in the course of the pulse train is not responsible for the contraction fade. Rather, the reason is a failure of the process by which the smooth muscle cell depolarization triggers action potentials. Inactivation of l-type Ca2+ channels that are under the control of released ATP may be the underlying mechanism.
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Correspondence to: B. Driessen at the above address
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Driessen, B., von Kügelgen, I., Bültmann, R. et al. The fade of the purinergic neurogenic contraction of the guinea-pig vas deferens: analysis of possible mechanisms. Naunyn-Schmiedeberg's Arch Pharmacol 350, 482–490 (1994). https://doi.org/10.1007/BF00173017
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DOI: https://doi.org/10.1007/BF00173017