Role of tachykinins in non-adrenergic non-cholinergic excitation in smooth muscles of the gastrointestinal tract

Abstract

Two peptides from the tachykinin family, substance P (SP) and neurokinin A (NKA), were identified as neurotransmitters (co-transmitters) of non-adrenergic non-cholinergic (NANCh) excitation in the gastrointestinal tract. The contraction of smooth muscles produced by tachykinins released from the excitatory enteric motoneurons is mediated by the NK1 and/or the NK2 tachykinin receptors. The differing contribution of these receptors in mediating the NANCh excitatory responses has been demonstrated in various regions of the intestine. The NK3 tachykinin receptors are confined only to the enteric neurons; they mediate release of different excitatory and inhibitory transmitters. The main secondary messenger pathway for all three tachykinin receptors is phosphoinositide breakdown that results in an increase of intracellular Ca2+ concentration. Signal transduction mechanisms are still not adequately known for tahykinin receptors. A multiple ionic mechanism has been proposed to mediate excitatory action of SP; it comprises activation of non-selective cationic channels, or activation of maxi Cl− channels, and/or inhibition of K+ channels. Data about the ionic mechanism underlying the NK2 receptor activation are still missing. In conclusion, SP and NKA play a physiological role as NANCh neurotransmitters in smooth muscles of the gastrointestinal tract and, therefore, tachykinins may have a significant pathophysiological relevance in humans.