Influence of denervation on smooth muscle response to repeated administration of cyclophosphamide, cytosine arabinoside, or their combination.
Cyclophosphamide, 40 mg.kg-1, cytosine arabinoside, 2 mg.kg-1 or their combination, were all given once weekly to chicks for 5 weeks. The expansor secundariorum muscle of the left wing of each chick was then surgically denervated leaving that of the right wing to serve as the control. Drug administrations continued for a further 5 weeks before the responses of normal and denervated expansor muscles were determined pharmacologically. Cyclophosphamide depressed the response of the expansor muscle to noradrenergic nerve stimulation but enhanced the response to noradrenaline and potassium chloride. Cytosine arabinoside enhanced responses of expansor muscles to noradrenergic nerve stimulation and noradrenaline, but depressed responses evoked by potassium chloride. The combination enhanced responses to nerve stimulation, noradrenaline, and potassium chloride. Expansor muscles were unresponsive to acetylcholine and anticancer drugs failed to restore the responsiveness to acetylcholine except the combination. Denervation depressed responses to noradrenergic nerve stimulation but caused supersensitivity to noradrenaline; this was more marked in the combination and cyclophosphamide groups, with no change in sensitivity seen in the cytosine arabinoside group. The denervated expansor muscle responded to acetylcholine in the order, combination much greater than cyclophosphamide greater than control greater than cytosine group. Denervated expansor muscles from anticancer groups were supersensitive to potassium chloride, with the combination group having the most pronounced effect. It is suggested that denervation influences smooth muscle sensitivity to agonist drugs which can modify the effects of anticancer drugs on smooth muscle.
Onwukeme
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Department of Pathology/Haematology, Faculty of Medical Sciences, University of Jos, Nigeria.
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Udoh
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D000320:Adrenergic Fibers / Q000187:drug effects / Q000502:physiology; D000818:Animals; D046508:Culture Techniques; D003520:Cyclophosphamide / Q000494:pharmacology*; D003561:Cytarabine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004576:Electromyography / Q000187:drug effects*; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects* / Q000502:physiology; D009121:Muscle Denervation; D009130:Muscle, Smooth / Q000187:drug effects / Q000294:innervation*; D009638:Norepinephrine / Q000502:physiology; D011930:Reaction Time / Q000187:drug effects / Q000502:physiology
D003561:Cytarabine; D003520:Cyclophosphamide; D009638:Norepinephrine