Nitric oxide mediating NANC inhibition in opossum lower esophageal sphincter

Abstract

Strips from opossum lower esophageal sphincter were prepared and mounted in organ baths for recording of isometric tension. Nonadrenergic, non-cholinergic (NANC) inhibitory responses were evoked by transmural field stimulation. The relaxant responses to field stimulation were inhibited in a concentration-dependent manner by N omega-nitro-L-arginine (L-NNA), a substance known to inhibit the formation of nitric oxide (NO). At a concentration at 10(-4) M of L-NNA, most preparations contracted during field stimulation, and this response was abolished by atropine (10(-6) M). L-Arginine (10(-5) M) shifted the concentration-response curve for L-NNA to the right. Relaxant responses to VIP (10(-9) to 10(-6)M) and sodium nitroprusside (10(-9) to 10(-5) M) were unaffected by preincubation with L-NNA (10(-5) to 10(-4) M) or L-arginine (10(-5) M). The inhibition of NANC-relaxation was apparently not due to an influence on release of a NANC transmitter different from NO, since L-NNA had no preserving effects on responses to field stimulation in preparations treated with scorpion venom. We conclude that involvement of a NO-generating process from L-arginine seems mandatory for NANC responses in the isolated lower esophageal sphincter.

A possible role of the L‐arginine‐nitric oxide pathway in the modulation of cholinergic transmission in the guinea‐pig taenia coli

“…Moreover, relaxant responses to forskolin and SNP, stimulators of adenylate and guanylate cyclase, respectively (Seamon et al, 1981;Rapoport & Murad, 1983), were unaffected by L-NNA preincubation, indicating that the inhibitory effect of L-NNA was not due to a direct effect on these enzymes. In this particular tissue, however, we found that the L-arginine-NO pathway apparently plays a less prominent role for relaxation, as L-NNA in the applied concentrations had a more pronounced effect on NANC-mediated relaxations in some other tissues studied (Li & Rand, 1989;Hobbs & Gibson, 1990: T0ttrup et al, 1991aT0ttrup et al, 1992). Further support is added to these considerations, as L-NNA did not shift the frequencyresponse curve, implying a non-competitive nature of L-NNA on inhibitory responses, and thus, suggesting the action of at least one other inhibitory NANC mediator.…”

Characterization of nerve-induced relaxation of gastrointestinal sphincteric smooth muscle in a South American opossum (Didelphis albiventris)

“…Following the description that the smooth muscle composition of the NA opossum lower esophageal sphincter, in contrast to that of more common laboratory animals (rats, cats and dogs), resembles more closely the human lower esophageal sphincter (13) most of the current concepts regarding the neural control of gastrointestinal sphincters were derived from in vivo and in vitro studies performed on this animal model (3)(4)(5)(6)(7)(8)14,15). Since this opossum species is not readily available to us, in the present study we characterized in vitro the nerve-induced responses of the circular smooth muscle from gastrointestinal sphincters of the closely related opossum species Didelphis albiventris, readily available in SA.…”

“…Evidence accumulated during the last three decades indicates that nerves mediating such responses employ neither noradrenaline nor acetylcholine as a neurotransmitter and consequently are referred to as nonadrenergic noncholinergic (NANC) nerves (2). Experiments designed to elucidate the mediator and mechanisms involved in NANC nerve-induced relaxations of sphincteric muscle in the gastrointestinal tract have been performed mainly in North American (NA) opossums (Didelphis virginiana) (3)(4)(5)(6)(7)(8) or in dogs (9)(10)(11)(12). The properties of opossum gastrointestinal sphincters are closer to the human ones as compared to dogs and cats (13) but NA opossums are not readily available in Brazil.…”

Regional functional specialization and inhibitory nitrergic and nonnitrergic coneurotransmission in the human esophagus

“…Enteric motoneurons (EMNs) are the final step in the inhibitory vagal pathway to the LES, mediating swallow-induced and transient LES relaxation (3). Nitric oxide (NO) released from these inhibitory EMNs is the major contributor to LES relaxation in humans (12) and opossums (20,33). However, vasoactive intestinal peptide (VIP) and ATP are putative inhibitory neurotransmitters in animal studies (14, 21-24, 34, 37, 39), and the relative contribution of each of these neurotransmitters remains unclear in humans.…”