Dependence of prejunctional beta-adrenoceptor facilitation of sympathetic neurotransmission on stimulus train length and agonist exposure time.

Prejunctional beta-adrenoceptors facilitate stimulus-induced neuronal norepinephrine release in the rat kidney. The mechanism(s) responsible for the bell-shaped concentration-facilitatory response curve to isoproterenol generated in the presence of alpha-adrenoceptor blockade and uptake blockade was explored. The concentration-response curve to isoproterenol generated using 30 pulses/stimulation and 20 min exposure to each agonist concentration was bell-shaped in nature, exhibiting a maximum response at 10 nM isoproterenol. Shortening the isoproterenol exposure time to 5 min for each concentration still resulted in a bell-shaped curve. Reducing the stimulus train length from 30 pulses to 10 pulses/stimulation failed to change the shape of the curve but produced a greater maximum response. However, shortening the isoproterenol exposure time to 2 min (10 pulses/stimulation) resulted in a curve which was not bell-shaped. These results suggest that prejunctional beta-adrenoceptors are susceptible to rapid desensitization upon prolonged agonist exposure and that an inverse relationship exists between stimulus train length and prejunctional beta-adrenoceptor-mediated facilitation.