Evidence for the involvement of both ATP and nitric oxide in non‐adrenergic, non‐cholinergic inhibitory neurotransmission in the rabbit portal vein

Abstract

The NANC inhibitory innervation of the longitudinal muscle of the rabbit portal vein has been examined. Neurogenic relaxations were partially inhibited by the P2-purinoceptor antagonist, suramin. Addition of the NO-synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME) also significantly reduced responses to electrical stimulation and the addition of L-arginine reversed this effect. A combination of both suramin and L-NAME abolished the neurogenic relaxation. A maximum relaxation of the vein was evoked by sodium nitroprusside which was not affected by L-NAME or suramin. Histochemical staining demonstrated the presence of NADPH-diaphorase containing nerves between the longitudinal and circular muscle coats of the media and also in the adventitia. It is concluded that both ATP and NO are inhibitory neurotransmitters in the NANC nerves of the rabbit portal vein.

Purinergic receptors in the splanchnic circulation

“…Functionally, neurogenic released ATP evokes biphasic responses on the vascular smooth muscle: initially direct excitatory junction potentials followed by indirect hyperpolarization through the release of endothelium-derived hyperpolarizing factor (EDHF) [172]. Interestingly, there is a report of ATP being partially responsible for the neurogenic NANC endothelium-independent relaxation of the longitudinal muscle of the rabbit portal vein [13]. This ATP-mediated neurogenic relaxation seems to come about via P2 receptors located on the smooth muscle [13,76].…”

“…Interestingly, there is a report of ATP being partially responsible for the neurogenic NANC endothelium-independent relaxation of the longitudinal muscle of the rabbit portal vein [13]. This ATP-mediated neurogenic relaxation seems to come about via P2 receptors located on the smooth muscle [13,76]. A study suggested that the sympathetic purinergic contractile responses of the dog mesenteric artery may be caused by an unknown substance selective to P2X-purinergic receptors, rather than ATP [114].…”

“…The P2Y 1 , P2Y 2 , P2Y 4 , P2Y 6 , P2Y 11 , P2Y 12 and P2Y 13 receptors are the mammalian receptors, while the P2Y 3 , P2Y 5 , P2Y 7 , P2Y 8 , P2Y 9 and P2Y 10 receptors represent receptors cloned from non-mammalian vertebrates or receptors that are currently under functional characterization [1]. Based on (1) sequence homology, (2) the presence of key amino acids essential for receptor activation, (3) chromosomal colocalization, (4) similarity of the cognate ligand, and (5) identification of uridine diphosphate (UDP)-glucose in the extracellular space, the IUPHAR Subcommittee recently rename the UDP-glucose receptor the P2Y 14 receptor [1].…”

“…However, there are no studies on this issue in what concerns the splanchnic circulation. Pharmacologically, P2Y receptors can be subdivided into the adenine-nucleotide-preferring receptors mainly responding to adenosine diphosphate (ADP) and ATP (human and rodent P2Y 1 , P2Y 12 and P2Y 13 , and human P2Y 11 ), the uracil-nucleotide-preferring receptors (human P2Y 4 and P2Y 6 ) responding to either uridine triphosphate (UTP) or UDP, receptors of mixed selectivity (human and rodent P2Y 2 and rodent P2Y 4 ), and receptors responding only to UDP-glucose and UDP-galactose (P2Y 14 ) [2].…”

Intrahepatic Flow Disturbance: Possibility of a Hidden Cause of Drug Toxicity

“…From studies on an extrahepatic portal vein preparation, various NANC transmitters have been proposed to control portal vein tone (41). In the rabbit portal vein, NO has been identified pharmacologically and histochemically as an inhibitory transmitter in NANC nerves (42). Elucidation of the distribution of NANC nerves along the intrahepatic portal venous tree, and hepatic arterial branches also, may help in understanding the neuronal regulatory mechanism of hepatic perfusion in more detail and may give further clues as to how to ameliorate intrahepatic flow disturbance.…”