Effects of theophylline and N6,O2-dibutyryl adenosine 3':5'-monophosphate on sympathetic ganglionic transmission in rats.
The effects of theophylline and N6,O2-dibutyryl adenosine 3':5'-monophosphate (DBcAMP) on the amplitude of the postganglionic action potential during and after a 10 Hz repetitive volley, and 50 to 1000 msec after a conditioning stimulus were investigated. The effects of both drugs on some electrophysiological properties of single cells of the isolated superior cervical ganglia of rats were also studied. At low concentrations of theophylline a reversible potentiation of the compound action potential occurred during and after repetitive stimulation at 10 Hz and also after the single conditioning stimulus. This effect was antagonized by atropine. Large concentrations of theophylline exerted a depressive effect only. Low concentrations of DBcAMP caused a reversible initial depression followed by a durable facilitation of transmission during repetitive stimulation. These concentrations potentiated the action potential amplitude after repetitive stimulation, but depressed it after a single conditioning stimulus. Atropine augmented the latter two effects. DBcAMP at large concentrations depressed transmission, but transmission was facilitated after drug washout. Theophylline and guanosine 3':5'-monophosphate, at ineffective concentrations when used singly, potentiated each other and elicited facilitation which was abolished by atropine. Theophylline and DBcAMP at these concentrations depolarized ganglion cells with a time course shorter than that of the aforementioned effects. Both drugs reduced the frequency and amplitude of the spontaneous miniature excitatory postsynaptic potentials. Theophylline did not increase the evoked transmitter release appreciably. On the basis of these findings and the evidence from literature, it is suggested that the reversible facilitatory effect of theophylline may be at least in part due to inhibition of phosphodiesterase of the ganglion cells leading to an enhanced muscarinic transmission. The prolonged facilitatory effect of DBcAMP may result from a durable change in the postsynaptic membrane structure leading to enhanced muscarinic transmission. An enhancement in the muscarinic transmission by both drugs increases the membrane excitability causing recruitment of subthreshold depolarized cells to discharge resulting in facilitation.
D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D006152:Cyclic GMP / Q000494:pharmacology; D004558:Electric Stimulation; D005725:Ganglia, Autonomic / Q000187:drug effects* / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D051381:Rats; D009435:Synaptic Transmission / Q000187:drug effects*; D013806:Theophylline / Q000494:pharmacology*
D003994:Bucladesine; D013806:Theophylline; D006152:Cyclic GMP; D000109:Acetylcholine