Modulation of non‐adrenergic non‐cholinergic inhibitory neurotransmission in rat gastric fundus by the α₂‐adrenoceptor agonist, UK‐14,304

Abstract

1 The influence of the X2-adrenoceptor agonist, UK-14,304, on non-adrenergic non-cholinergic (NANC) relaxation induced by electrical field stimulation was investigated in longitudinal muscle strips of the gastric fundus of reserpinized rats.2 In tissues where tone was raised by 3 x l0' M prostaglandin F2, (PGF2.), the inhibitory effect of 10-6 M UK-14,304, on the NANC relaxations induced by short train stimulation (40 V, I ms, 20 s) was inversely related to the stimulus frequency (1-4-16 Hz). UK-14,304 (10-6 M) did not influence relaxations induced by administration of exogenous nitric oxide (NO, 2 x 10-6 M-10-4 M). The inhibitory effect of UK-14,304 on the electrically induced relaxations was antagonized by 10-6 M rauwolscine but not by 10-6 M prazosin. 3 UK-14,304 (10-6 M) also reduced the amplitude of the sustained NANC relaxation, induced by electrical field stimulation (40 V, 1 ms, 4 Hz) for 5 min. The effect of UK-14,304 was also antagonized by 10-6 M rauwolscine but not by 10-6 M prazosin. UK-14,304 (10-6 M) did not reduce the relaxation induced by 3 x 10-M vasoactive intestinal polypeptide (VIP). 4 These results suggest that the release of the inhibitory NANC neurotransmitter during short train stimulation, thought to be NO, and during sustained stimulation, thought to be VIP, is inhibited by stimulation of presynaptic x2-adrenoceptors in the rat gastric fundus.

α2‐Adrenoceptor‐mediated modulation of the nitrergic innervation of the canine isolated ileocolonic junction

“…Prejunctional modulation of NANC neurotransmission in the gastrointestinal tract was previously decribed in only a few tissues (see Introduction); in the rat gastric fundus (Mac-Donald et al, 1990) and the guinea-pig proximal colon (Kojima et al, 1988), the prejunctional inhibition of the NANC relaxations was reported to be mediated by (X2adrenoceptors. Recently Lefebvre & Smits (1992) showed in the rat gastric fundus that UK-14,304 blocked the NANC relaxations induced by short train stimulation, previously demonstrated to be mediated by NO (Li & Rand, 1990;Boeckxstaens et al, 1991a), suggesting prejunctional inhibition of NO release via M2-adrenoceptor activation. In contrast to our results, clonidine did not affect the NANC relaxations in the rat gastric fundus.…”

“…Recently Lefebvre & Smits (1992) Lefebvre, 1988), complicating the study of prejunctional regulation of NO release.…”

“…This knowledge, together with morphological evidence demonstrating the presence of NO synthase in its myenteric neurones (unpublished observations), make the ileocolonic junction an interesting model to study possible prejunctional regulation of NO release. Since the ileocolonic junction receives a prominent adrenergic innervation and since prejunctional modulation of NANC neurotransmission via adrenoceptors has been described (Kojima et al, 1988;MacDonald et al, 1990;Lefebvre & Smits, 1992), we suggest a possible prejunctional adrenergic regulation of the NO release at the canine ileocolonic junction.…”

“…However, evidence suggesting this concept in the peripheral nonadrenergic non-cholinergic (NANC) nervous system, and especially the nitrergic innervation, is rather scarce. In the gastrointestinal tract, prejunctional inhibition of NANC neurotransmission has only been demonstrated in the rat gastric fundus (MacDonald et al, 1990; Lefebvre & Smits, 1992), the guinea-pig proximal colon (Kojima et al, 1988), the rat anococcygeus muscle (Li & Rand, 1989), and the canine lower oesophageal sphincter (Barnette et al, 1990).…”

VIP‐ and PACAP‐mediated nonadrenergic, noncholinergic inhibition in longitudinal muscle of rat distal colon: involvement of activation of charybdotoxin‐ and apamin‐sensitive K+ channels

“…PACAP638 also significantly inhibited the ij.ps. (Grider et al, 1985), rat (Li & Rand, 1990;Lefebvre & Smits, 1992) and pig (Lefebvre et al, 1995) gastric fundus, the rabbit (Biancani et al, 1985) and opossum (Goyal et al, 1980;Nurko & Rattan, 1988) lower oesophageal sphincter, and the chicken rectum (Komori & Ohashi, 1990). Charybdotoxin has also been reported to inhibit nitric oxide-independent relaxation in rabbit abdominal aorta and carotid artery (Cowan et al, 1993), and to inhibit partly the nitric oxide-induced relaxation in rabbit aortic smooth muscle cells (Bolotina et al, 1994).…”