1 We aimed to characterize 5-HT receptors mediating contraction and relaxation to 5-HT in dog proximal stomach longitudinal muscle (LM) strips.2 Of the tryptamine analogues tested, 5-HT was the most potent contractile agent at basal length, while 5-CT was the most potent relaxant of PGF 2a -induced contraction. Neither the contractions to 5-HT, nor the relaxations to 5-CT were in¯uenced by tetrodotoxin, illustrating that action potential propagation is not involved. 3 The 5-HT-induced contraction was antagonized by mesulergine (0.03 to 0.3 mM) and ketanserin (2 ± 20 nM), but the antagonism was not of a simple competitive nature, indicating multiple receptor involvement. Ketanserin (3 to 30 nM) and mesulergine (30 nM) competitively antagonized the a-Me-5-HT-induced contraction (pK B : 8.83+0.09 and pA 2 : 8.25+0.06 respectively). These a nity values are in line with literature a nities of ketanserin and mesulergine at 5-HT 2A receptors in various bioassays. 4 The 5-CT-induced inhibition of PGF 2a -induced contraction was competitively antagonized by mesulergine (pK B estimate: 8.52+0.12) and by the selective 5-HT 7 receptor antagonist SB-269970 (pK B estimate: 9.36+0.14). Both pK B estimates are in line with literature a nities of these compounds for 5-HT 7 receptors. Mesulergine (30 nM) and SB-269970 (10 nM) shifted the relaxant curve to 5-HT parallel to the right in the presence of ketanserin (0.3 mM) (pA 2 estimates of 8.08+0.10 and 8.75+0.14 respectively), indicative of 5-HT 7 receptor involvement. 5 It is concluded that 5-HT induces dog proximal stomach (LM) contraction via smooth muscle 5-HT 2A receptors and relaxation via smooth muscle 5-HT 7 receptors.

In vitro studies showed that relaxations induced after vagal stimulation of the guinea pig stomach are mediated via nitric oxide (NO). The role of NO in canine gastric relaxation in response to vagal stimulation has as yet not been studied. The present study examined the influence of NG-nitro-L-arginine (L-NNA) on gastric relaxations after vagal nerve stimulation in the anesthetized dog. In beagle dogs (n = 7), the ventral and dorsal abdominal vagal nerves were connected to a pair of platinum electrodes. Gastric tone was measured by means of a barostat. Changes in gastric motility were measured with force transducers sutured on the fundus and the antrum. The cervical vagi were sectioned, and dogs were given atropine (0.2 mg/kg i.v.) and guanethidine (5 mg/kg i.v.). Electrical stimulation of the vagal trunks (19 V, 1-ms duration, for 15 s every 2 min, 1-30 Hz) induced frequency-dependent increases in volume. On the fundus, frequency-dependent relaxations could be observed (maximal effect at 5 mmHg and at 10 Hz). During electrical stimulation, the spontaneous antral contractions were completely blocked. After cessation of the stimulus, "rebound" contractions could be observed. L-NNA (5 mg/kg i.v.) completely blocked the increases in gastric volume and the relaxations on the fundus. On the antrum, however, contractions were observed during the electrical stimulation. L-Arginine (250 mg/kg i.v.) gradually restored the relaxations on electrical stimulation. This study demonstrates that NO mediates short-lasting vagally induced gastric relaxations in the anesthetized dog.

intraduodenal administration of intralipid induces a gastric relaxation via a NO-dependent mechanism.

No abstract

Acute psychological stress, which could be related to the release of a large amount of catecholamines, may cause oesophageal motility disorders. Therefore, the aim of our study was to elucidate the influence of adrenoceptor agonists on the striated muscle portion of the oesophagus by use of isolated strips from dogs. Contractions were evoked in isolated striated muscle strips by electrical field stimulation (1 pulse min−1, 1 ms/pulse, submaximal voltage). The effects induced by administration of adrenoceptor agonists alone or in the presence of antagonists were tested to determine the nature of the adrenoceptors on this muscle preparation. The administration of both the natural adrenoceptor agonists, adrenaline and noradrenaline, and the synthetic β‐adrenenoceptor agonists, isoprenaline (β1 + β2), dobutamine (β1) or ritodrine (β2), enhanced the amplitude of the contractions induced by electrical stimulation in a concentration‐dependent manner. The maximum responses were 82.6 (adrenaline), 66.2 (noradrenaline), 86.2 (isoprenaline), 34.6 (dobutamine) and 80.8% (ritodrine). The EC20 values obtained were respectively 2 nm, 0.2 μm, 0.91 nm, 3 μm and 80 nm. The administration of the α1‐adrenoceptor agonist, phenylephrine, also enhanced the contractile response in a concentration‐dependent manner (EC20 value = 0.3 μm) and the maximum response was 64.6%, but the administration of the α2‐adrenoceptor agonist, clonidine, did not influence the contractile response. These data suggest the involvement of β2‐ and possibly α1‐adrenoceptors in the responses of these adrenoceptor agonists. The selective β2‐adrenoceptor antagonist ICI 118551 (3–100 nm) shifted the concentration‐effect curves for noradrenaline, phenylephrine and ritodrine to the right in a concentration‐dependent manner. ICI 118551 (3 nm) also shifted the concentration‐effect curves for adrenaline and isoprenaline to the right, but increasing the concentration of ICI 118551 did not cause any further antagonist activity until a concentration of 100 nm, when a further rightward shift was obtained. The selective α1‐adrenoceptor antagonist, prazosin (30–300 nm), did not affect the increased contractile responses induced by adrenaline, noradrenaline, phenylephrine, isoprenaline or ritodrine. In conclusion, it appears that β2‐adrenoceptors are present in the striated muscle portion of the canine oesophagus, where they mediate an enhancement of contractile responses evoked by electrical stimulation. The α1‐agonist, phenylephrine, appears to interact with β2‐adrenoceptors on this preparation. β3‐Adrenoceptors have already been demonstrated in smooth muscle from various parts of the gastrointestinal tract, and our study does not exclude the possibility that there is an additional population of β3‐receptors in the canine striated muscle part of the oesophagus.