PRESENCE AND EFFECTS OF PITUITARY ADENYLATE-CYCLASE ACTIVATING PEPTIDE IN THE SUBMANDIBULAR-GLAND OF THE FERRET

Pituitary adenylate cyclase activating peptide (PACAP), a recently des cribed vasoactive intestinal peptide-like neuropeptide, was found to b e present in neurons in the submandibular gland of the ferret, where P ACAP-immunoreactive nerve fibres were distributed around blood vessels , acini and ducts. Most of the PACAP-immunoreactive fibres were distin ct from those storing vasoactive intestinal peptide. PACAP occurs in t issues as PACAP1-38 and PACAP1-27. PACAP1-38 and PACAP1-27 but not PAC AP16-38 displayed biological activity with about the same potency. The y exerted vasodilator effects on the submandibular vasculature, which resulted in a greater fall in vascular resistance than an equimolar do se of vasoactive intestinal peptide. The vasodilator response was inde pendent of muscarinic receptor activation. Neither vasoactive intestin al peptide nor PACAP alone evoked any flow of saliva. However, both va soactive intestinal peptide and PACAP enhanced the fluid response to a cetylcholine, and the flow of saliva as well as the output of protein in response to parasympathetic nerve stimulation, vasoactive intestina l peptide being more potent than PACAP. In vitro, protein was released from submandibular gland tissue in response to both vasoactive intest inal peptide and PACAP, vasoactive intestinal peptide being more poten t than PACAP. PACAP (and vasoactive intestinal peptide) exerted its in vitro effect following adrenoceptor and muscarinic blockade and follo wing degeneration of sympathetic nerves. Sympathetic denervation combi ned with parasympathetic preganglionic denervation resulted in superse nsitivity to both vasoactive intestinal peptide and PACAP. The fact th at PACAP and vasoactive intestinal peptide occur in different nerve fi bre populations suggests different functional roles for the two peptid es in the submandibular gland. The difference in potency between vasoa ctive intestinal peptide and PACAP with respect to vascular and secret ory responses suggests that the two peptides act on different receptor s and that PACAP is preferentially involved in the control of blood fl ow.