Journal of Neuroscience, Vol 5, 1947-1954, Copyright © 1985 by Society for Neuroscience
Regulation of the concentration of adenosine 3',5'-cyclic monophosphate and the activity of tyrosine hydroxylase in the rat superior cervical ganglion by three neuropeptides of the secretin family
NY Ip, C Baldwin and RE Zigmond
Preganglionic nerve stimulation leads to an acute elevation of tyrosine
hydroxylase (TH) activity in the rat superior cervical ganglion. This
effect is mediated in part by acetylcholine, acting via nicotinic
receptors, and in part by a noncholinergic neurotransmitter. As a first
step in an attempt to identify this noncholinergic transmitter, we have
examined a number of biogenic amines, purine nucleotides, neuropeptides,
and other compounds for their ability to increase TH activity. Secretin,
vasoactive intestinal peptide (VIP), and PHI (a 27- amino acid peptide with
an NH2-terminal histidine and a COOH-terminal isoleucine amide), all
members of the secretin family of peptides, increased TH activity acutely.
Human pancreatic growth hormone- releasing factor, glucagon, and gastric
inhibitory peptide (three other members of this peptide family) and all
other transmitter candidates tested had no effect on this enzyme activity.
We have examined the possibility that this peptidergic regulation of TH
activity is mediated via changes in adenosine 3',5'-cyclic monophosphate
(cAMP) levels. When the six members of the secretin family were tested for
their ability to increase cAMP levels in the ganglion, secretin, VIP, and
PHI significantly increased this cyclic nucleotide, whereas growth hormone-
releasing factor, glucagon, and gastric inhibitory peptide produced no
significant effects. The rank orders of potency and of efficacy of
secretin, VIP, and PHI in altering TH activity and cAMP levels were
identical. Furthermore, a strong correlation was found between the cAMP
level and the TH activity in individual ganglia exposed to these peptides.
Finally, 8-bromoadenosine 3',5'-cyclic monophosphate and forskolin also
increased TH activity.(ABSTRACT TRUNCATED AT 250 WORDS)