ICS 1999, Denver
Informally discussed posters
Pharmacology
PREJUNCTIONAL ALPHA-1 ADRENERGIC RECEPTORS INHIBIT NITRERGIC NEUROTRANSMISSION IN RABBIT URETHRA

M. Yoshida, A. Inadome, M. Yono, H. Seshita, Y. Miyamoto, S. Ueda
Department of Urology, Kumamoto University School of Medicine, Kumamoto, Japan

It has been confirmed that nitric oxide (NO) released from nitrergic nerve relaxes urethral smooth muscles (1,2). Recent studies have shown that the release of NO from vasodilator nerve can be inhibited through prejunctional either muscarinic or alpha adrenergic receptors in several vascular vessels (3, 4). However evidence is available about prejunctional modulation of nitrergic neurotransmission in urethral smooth muscles. The purpose of the present study was to investigate whether prejunctional alpha adrenergic receptors infill neurogenic relaxation of rabbit urethral smooth muscle.

Female New Zealand white rabbits weighing 2.5 kg were killed by exanguination after intravenous injection of sodium pentobarbital. The urethra were removed out through an abdominal midline incision. The urethral strip was suspended in a 20 ml muscle bath filled with Krebs-Henseleit solution, was connected to an isometric force displacement transducer, and an isometric tension development was recorded. Electrical field stimulation (0.5 msec pulse duration, 0.1-15 Hz and 3 sec train) was applied to urethral preparations precontracted with 0.1 microM endothelin-1. The microdialysis probe (O-P-100-10, Eikom, Kyoto, Japan) was inserted into the strip. Krebs-Henseleit solution was perfused into the probe at a rate of 2 microl/min. The dialysate during EFS (0.5 msec duration, 7 Hz, 3 sec train and 1 min interval for 10 min) was collected. A volume of 10 microl of the each sample was injected into the NOx analyzer, and the amount of NO₂^-/NO₃^- released in the dialysate was measured on the Greiss method, as reported previously (5). The effects of alpha adrenergic antagonists (prazosin and yohimbine) on the relaxation responses and NO₂^-/NO₃^- releases induced by EFS were eveluated.

Results

In the presence of guanethidine (10 microM) and atropine (1 microM), EFS caused relaxation responses and NO₂^-/NO₃^- releases in the rabbit urethral strips precontracted with endothelin-1. The relaxation responses and NO₂^-/NO₃^- releases were significantly inhibited in the presence of L-NNA (100 microM) or tetrodotoxin (1 microM). Pretreatment with prazosin (0.01 – 1 microM) and yohimbine (0.1 - 10 microM) did not cause significant effect on endothelin-1-induced contractions in the rabbit urethral strips. Pretreatment with prazosin caused dose-dependent increases relaxation responses and NO₂^-/NO₃^- releases induced by EFS in the rabbit urethral strips. While, pretreatment with yohimbine decreased the relaxation responses and NO₂^-/NO₃^- releases induced by EFS (Table 1)

Table 1 Effects of prazosin (1 microM) and yohimbine (10 microM) on EFS-induced relaxation responses and NO₂^-/NO₃^- (NOx) releases in the rabbit urethra

* Significantly different from the comparable value for control (p < 0.05).

Conclusions

The present data suggest that the relaxation responses mediated by NO released from nitrergic ner rabbit urethra are enhanced and inhibited by blockade of prejunctional alpha-1 and alpha-2 adrenergic receptors, respectively.

References

1) Life Sic. 48: 2429-2436, 1991
2) Eur. J. Pharmacol. 357: 213-219, 1998
3) J. Urol. 157: 2356-2360, 1997
4) Neuroscience 54: 819-825, 1993
5) Eur. J. Pharmacol. 339:165-171, 1997