Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: CAS:58-74-2 (Papaverine)
 470 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. The effect of papaverine, a well known smooth muscle relaxant, was investigated on neural transmission within the enteric nervous system. Segments of guinea-pig ileum were placed in a partitioned bath to enable drugs, including papaverine, to be applied to enteric nerve pathways without interfering with the recording of the smooth muscle contraction. Ascending excitatory enteric nerve pathways were activated by electrical field stimulation in the anal compartment (10 Hz for 2 s, 45 mA, 0.5 ms pulse duration) and the resulting contraction of the intestinal circular muscle in the oral compartment was recorded isotonically. 2. Tetrodotoxin (0.6 microM) and hexamethonium (100 microM) both abolished, or greatly reduced, the contractions when applied to either compartment indicating that nicotinic synapses are involved in this pathway. 3. Papaverine (0.3-30 microM) applied independently to each compartment depressed in a concentration-dependent manner, the nerve-mediated contractions. The IC50 of this inhibitory effect was 3.53 microM for the oral and 4.76 microM for the anal compartments, respectively. Two other phosphodiesterase (PDE) inhibitors, 3-isobutyl-1-methylxanthine (IBMX 10-300 microM) and theophylline (30-1000 microM) added to the anal compartment also inhibited the nerve mediated contractions. Papaverine applied to the anal bath, after IBMX 100 microM (or theophylline 300 microM) further inhibited the nerve-mediated contractions, but was less effective than when applied alone. 4. Phentolamine (1 microM), an alpha-adrenoceptor antagonist, reduced the inhibitory effect of papaverine, but not that of IBMX (100 microM) or theophylline (300 microM). A combination of phentolamine and IBMX (or theophylline) prevented the inhibitory effect of papaverine. 5. Tetrodotoxin, but not papaverine or hexamethonium, inhibited the contraction elicited by electrical stimulation just anal to the partition indicating that papaverine did not affect the generation or conduction of nerve action potentials. 6. Verapamil (1 microM) and nifedipine (1 microM), two smooth muscle relaxants which act by blocking L-type calcium channels, only inhibited the contractions when applied directly to the recording (oral) compartment. This indicates that L-type Ca2+ channels are probably not involved in synaptic transmission in these ascending pathways and thus that the PDE inhibitors do not inhibit synaptic transmission by acting on these channels. omega-Conotoxin GVIA (10 nM), a potent inhibitor of the N-type Ca2+ channels, blocked the nerve-mediated contractions applied to either compartment. Whether the PDE inhibitors exert their inhibitory actions via these channels remains to be established. 7. The results indicate that the PDE inhibitors, papaverine, IBMX and theophylline inhibit excitatory enteric neural pathways by depressing synaptic transmission. The inhibitory effect of papaverine (but not IMBX or theophylline) involves, at least in part, the release of noradrenaline from sympathetic nerves acting on alpha-adrenoceptors on enteric neurones.
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PMID:Effect of papaverine on synaptic transmission in the guinea-pig ileum. 920 46

The present study was carried out compare the effects of nifedipine, verapamil, papaverine and chloroethylclonidine (CEC) on the electrically-induced contractions and on the contractions produced by exogenous noradrenaline and alpha, beta methylene-ATP in the epidydimal portion of rat vas deferens. Nifedipine inhibited in a concentration-dependent fashion the purinergic component (phase I) of the electrically evoked response. Verapamil (10(-7) M-10(-5) M) did not inhibit significantly or even potentiated phase I of the contractile response to single-pulse field stimulation but inhibited the response to alpha,beta methylene-ATP. Papaverine left unaffected phase I but depressed the response to alpha,beta methylene-ATP. CEC significantly potentiated the purinergic component of the electrically-evoked response and the response induced by alpha,beta methylene-ATP. Nifedipine was devoid of any inhibitory action on the noradrenergic component (phase II) of the response to single shock. Verapamil at the highest concentration used (10(-5) M) was able to partially inhibit phase II. Papaverine abolished in a concentration-dependent manner the noradrenergic component of the response to single shock. CEC abolished the phase II of single shock while was devoid of any inhibitory action on exogenous noradrenaline. The implications of these differences among the compounds studied in the present work are discussed in relation to roles of calcium channels.
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PMID:Differential blockade of alpha,beta-methylene-ATP, noradrenaline and electrically evoked contractions of the rat vas deferens. 1058 76

1. Frequency-response curves (0.1-30 Hz) were obtained in the epididymal portion of rat vas deferens. At low frequencies (0.1-1 Hz), the parameters evaluated were the first twitch and the fourth twitch at each frequency. The responses to trains of stimuli at intermediate (2-5 Hz) and high (10-30 Hz) frequencies were biphasic consisting of phase I (the first rapid phase of tetanus) and of phase II (the secondary slowly developing one). 2. Prazosin inhibited the first and the fourth twitch but not when the frequency was < 1 Hz. Suramin inhibited the first twitch while substantially depressing the fourth one. The combination of prazosin and suramin almost completely abolished all the twitches evoked by a train of stimuli at low frequencies. Nifedipine left almost unaltered the first twitch while markedly depressing the fourth one, especially at relatively high frequency (1 Hz). Verapamil was devoid of any inhibitory action. Papaverine depressed the first twitch while only at the highest concentration used (1 x 10(-4) M) markedly inhibited the fourth one. Chloroethylclonidine (CEC) depressed the first twitch and increased the fourth. 3. When intermediate (2-5 Hz) and high (10-30 Hz) frequencies are considered, prazosin and suramin partially inhibited both phase I and phase II, while in combination they almost completely abolished both phases. Nifedipine and verapamil selectively suppressed phase II, leaving phase I unaffected. Papaverine completely abolished both phase I and phase II. CEC was able to completely abolish phase I but increased phase II. 4. These results suggest that the response to the first twitch of a train at low frequency is prevailingly noradrenergic, prazosin-sensitive, while when the twitches are close enough (i.e. at 1 Hz) a summation of stimuli takes place and a predominant purinergic component, both suramin- and nifedipine-sensitive, becomes evident. 5. At high frequencies, both phases are due to the concomitant release of noradrenaline and adenosine triphosphate (ATP). The noradrenergic component of phase I is nifedipine-insensitive and CEC-sensitive, resembling the pharmacological profile of the endogenously released noradrenaline by single pulse, while that of phase II, nifedipine-sensitive and CEC-insensitive, is similar to that produced by exogenously applied noradrenaline.
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PMID:Differential effects of drugs interacting with autonomic transmitters on responses of rat vas deferens to field stimulation. 1109 47


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