Intracisternal administration of avian pancreatic polypeptide lowers respiration rate and enhances the clonidine induced reduction of respiration rate in α‐chloralose anesthetized rats: Possible interactions with an α2‐adrenergic receptor

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Abstract
Avian pancreatic polypeptide (APP) is a 36 amino acid peptide isolated from chicken pancreas (Kim‐mel et al. 1975) and there exists a wide‐spread distribution of APP‐like immunoreactive nerve cell bodies and terminals in the central and peripheral nervous systems (Lorén et al. 1979, Hökfelt et al. 1981). Furthermore, it has recently been discovered (Lundberg et al. 1980a) that an APP‐like immunoreactive substance (Kimmel et al. 1975) is present in central phenylethanolamine‐N‐methyltransferase (PNMT) immunoreactive neurons and in some noradrenaline (NA) neurons. Thus, an APP‐like peptide and adrenaline (A) may coexist in some A nerve cells in the central nervous system (see also Hunt et al. 1981). This coexistence appears to exist in A nerve cells of both cell groups C1 and C2 (Hökfelt et al. 1974, Lundberg et al. 1980a). Evidence exists that many of the A neuron systems of the brain represent vasodepressor pathways, and it has been suggested that clonidine may produce at least part of its hypotensive actions via activation of postsynaptic α2‐adrenergic receptors linked to A synapses in the brain, especially in the medulla oblongata (Bolme et al. 1974, Fuxe et al. 1975, Fuxe et al. 1980). It has also been suggested that certain A neurons regulate respiration rate and the clonidine induced reduction of respiration rate may therefore at least in part be mediated via α2‐adrenergic receptors linked to A synapses in the medulla oblongata (Bolme et al. 1974). In order to understand the possible functional significance of co‐storage of APP‐like material and A we have now investigated the effects of APP and for comparison also bovine pancreatic polypeptide (BPP) (Chance & Jones 1974), which differ in only one or two positions from other mammalian forms of the peptide, on cardiovascular parameters and on respiration rate and on clonidine induced reduction of arterial blood pressure and respiration rate. BPP differs in 21 positions from APP, but BPP‐like and APP‐like immunoreactive neurons are distributed in the rat brain in a similar way and seem to represent one and the same neuronal system (Ol‐schowska et al. 1981). Thus, APP/BPP‐like immunoreactive material exists in the A neurons, but its exact identity is unknown.