Effects of acute and long-term atropine treatment on levels, release and response to VIP and PHI in the submandibular gland of cat and rat.
We have studied the effects of acute and long-term treatment of cats and rats with atropine on the levels, release and effects of two peptides, vasoactive intestinal polypeptide (VIP) and peptide histidine isoleucine (PHI), that probably co-exist with acetylcholine in the parasympathetic nerves supplying the submandibular gland. Atropine treatment (progressively increasing doses from 2 to 15 mg kg-1 injected s.c.) for 14 days did not alter the contents of VIP- or PHI-like immunoreactivity (-IR) in the cat submandibular gland or in three other tissues (nasal mucosa, trachea and tongue). Acute as well as long-term atropine treatment decreased the vasodilation following low-, but not high-, frequency parasympathetic nerve stimulation. During prolonged stimulation (60 min) there was a decreased vasodilatation response following both acute and long-term atropine treatment. The overflow of VIP-IR and PHI-IR following parasympathetic nerve stimulation was markedly increased by acute, but not by long-term atropine treatment. The VIP- or PHI-induced stimulation of cyclic AMP (cAMP) accumulation in the cat submandibular gland was not altered after long-term atropine treatment. Similarly, treatment of male Sprague-Dawley rats with atropine (20 mg kg-1) or imipramine (20 mg kg-1) for 14 days did not alter the sensitivity to VIP or to PHI of cAMP accumulation in the submandibular gland, nor was there any change in VIP-IR or PHI-IR content. In conclusion, although atropine treatment causes an acute increase in the overflow of VIP and PHI evoked by parasympathetic nerve stimulation, there is no depletion of peptide stores upon long-term treatment, nor is there any change in the effect of exogenous VIP and PHI on cAMP-accumulation.
Dunér-Engström
M
M
Department of Pharmacology, Karolinska Institute, Stockholm, Sweden.
Larsson
O
O
Fredholm
B B
BB
Lundblad
L
L
Fahrenkrug
J
J
Lundberg
J M
JM
D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D001285:Atropine / Q000494:pharmacology*; D002415:Cats; D000242:Cyclic AMP / Q000378:metabolism; D006160:Guanosine Triphosphate / Q000378:metabolism; D007099:Imipramine / Q000494:pharmacology; D008297:Male; D009929:Organ Size / Q000187:drug effects; D010275:Parasympathetic Nervous System / Q000187:drug effects / Q000378:metabolism; D010451:Peptide PHI / Q000097:blood*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013363:Submandibular Gland / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D014660:Vasoactive Intestinal Peptide / Q000097:blood*
D010451:Peptide PHI; D014660:Vasoactive Intestinal Peptide; D001285:Atropine; D006160:Guanosine Triphosphate; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; D007099:Imipramine