Modulation of cholinergic neurotransmission by vasoactive intestinal peptide and peptide histidine isoleucine in guinea-pig tracheal smooth muscle.

There is increasing evidence that vasoactive intestinal peptide (VIP) and peptide histidine isoleucine (PHI) are non-adrenergic, non-cholinergic (NANC) inhibitory neurotransmitters in airway smooth muscle. The possibility that VIP and PHI may also have neuromodulatory effects on excitatory responses, mediated by cholinergic nerves, to electrical field stimulation (EFS) was studied in guinea-pig isolated trachea. VIP (0.5 nM) pre-junctionally, inhibited the release of acetylcholine (ACh), whereas post-junctionally, responses to methacholine (MCh) were enhanced. At a maximum relaxant concentration (100 nM), VIP inhibited cholinergic neurotransmission both pre- and post-junctionally. Similarly, PHI (30 nM) inhibited neuronal ACh release, but enhanced transmitter action post-junctionally. At 3 microM, PHI inhibited ACh release. VIP- and PHI-induced inhibition of EFS was not affected by methysergide, pyrilamine, naloxone, phentolamine and propranolol. These data suggest that, in airway smooth muscle VIP and PHI may modulate cholinergic transmission via specific receptors.