Characteristics of the axonal transport of vasoactive intestinal polypeptide (VIP) in nerves of the cat.

The axonal transport of vasoactive intestinal polypeptide (VIP) was examined in anesthetized cats. The distally directed (anterograde) flux of peptide was found to be about 35 fmol/h in the sciatic nerve. A smaller retrograde flux (8.5 fmol/h) weas also detected. In ulnar, radial and sciatic nerves, the average velocity of transport was calculated to be 2.5 mm/h in the anterograde and 0.6 mm/h in the retrograde direction. Clearance experiments indicated that the amounts of peptide available for transport in these two phases were 28% and 15% of the total, respectively. Estimates of true velocity based on these figures are 9 mm/h for anterograde transport and 4 mm/h for retrograde transport. Local injections of vinblastine were found to induce marked local increases in VIP-immunoreactivity, indicating that microtubules play a role in peptide transport. Subcellular distribution experiments showed that most of the transported VIP was associated with a particulate fraction, possibly corresponding to large vesicles. Only one molecular form of VIP-immuno-reactivity was detected by gel permeation chromatography and no evidence was obtained for cleavage of VIP precursors in the axon. Comparison of axonal flux of peptide with the apparent content of VIP in terminal regions indicated that the turnover time for this peptide is 5 days or longer in the periphery. The results are consistent with the view that peripheral neurons are dependent upon rapid axonal transport for the supply of vip to their terminals.