SUMMARY1. In chloralose-urethane-anaesthetized dogs a manometric assembly was inserted via a gastrostomy to monitor pyloric pressure with a sleeve sensor. Antral and duodenal contractions were monitored with both manometric side holes and serosal strain gauges.2. Subserosal silver wire electrodes were placed in the antrum 5 cm orad and the duodenum 3 cm aborad to the pylorus to facilitate field stimulation of intramural nerves.3. The pylorus exerted spontaneous tone (10-8 + 4-8 mmHg) with phasic contractions occurring at a rate varying from 1-5 min-' and, at times, with a superimposed higher frequency up to 15 min-. Atropine (30 4g kg-1 i.v. and 10,g I.A.) reduced and tetrodotoxin (50-100 jug I.A.) enhanced the phasic activity significantly.4. Bilateral cervical vagal section had no consistent influence on pyloric motility. 5. Stimulation of the distal ends of the cervical vagal nerves at low frequencies (0-2-0-5 Hz, 1-3 ms, 20 V) induced phasic pyloric contractions, which were abolished by atropine or hexamethonium (10 mg kg-' i.v. and 1 mg I.A.). Higher frequencies (> 0 7 Hz) of stimulation inhibited both phasic and tonic contractions and this inhibition was unaffected by atropine, hexamethonium, phentolamine (1-5 mg kg-' i.v. and 100 jtg I.A.) or propranolol (1 mg kg-' i.v. and 100 jug I.A.). All neural responses were blocked by tetrodotoxin (50-100 ,ug I.A.).6. Duodenal field stimulation (0-2-5 Hz, 0 5 ms, 40 V) induced strong phasic and tonic contractions in the pylorus. This excitation was blocked by atropine, hexamethonium, tetrodotoxin (50-100 ,ug I.A.) or duodenal transection orad to the stimulating electrodes.7. Antral field stimulation (05-1 Hz, 0-5 ms, 40 V) completely abolished phasic activity in the pylorus and reduced tonic activity, regardless of whether the contractile activity was spontaneous or induced by neural stimulation. This inhibitory action was unaffected by atropine, hexamethonium or propranolol but was blocked by tetrodotoxin and antral transection aborad to the stimulating electrodes. Phentolamine attenuated the inhibitory effect of antral field stimulation on pyloric motility.H.-D. ALLESCHER AND OTHERS 8. It is concluded that the distal canine pylorus exhibits myogenic tone and phasic activity which is modulated by extrinsic and intrinsic nerve pathways. Vagal nerves contain fibres, activated by different stimulus parameters which can either excite or inhibit pyloric activity. Activation of antral nerves inhibits pyloric activity, with both non-adrenergic, non-cholinergic and phentolamine-sensitive pathways contributing to this inhibitory response. Activation of duodenal intrinsic nerves activates a chain of orally projecting cholinergic nerves which enhances pyloric activity. The pyloric muscle should be considered as a sphincter because of its myogenic activity and special neural control.

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In 18 anesthetized dogs, antroduodenal and pyloric motility was monitored in vivo by a sleeve and perfused side-hole manometric assembly and by antral and duodenal serosal strain gauges. Close intra-arterial injection to the pylorus of dynorphin-(1-13) (Dyn) for kappa-receptors, [D-Pen2,5]enkephalin (DPen2,5-Enk) for delta-receptors, and [N-Me-Phe3-D-Pro4]morphiceptin (PL017) and [D-Ala2,N-Me-Phe4,Gly5-ol]enkephalin (DAGO) for mu-receptors showed no excitatory effect in the pylorus. When pyloric motor activity was increased by duodenal field stimulation 3-5 cm aboaad from the pylorus, Dyn greater than DPen2,5-Enk greater than DAGO produced a dose-dependent inhibition of the pyloric motor activity. Naloxone (200 micrograms/kg iv and 20 micrograms ia) had no effect on the pyloric excitation due to duodenal field stimulation, but it reduced the inhibitory response of intra-arterially injected opioids. In addition, opioid binding ([3H]diprenorphine) in microsomal and mitochondrial fractions from the inner circular muscle ring of the pylorus showed a distribution similar to the neuronal marker [3H]saxitoxin but no correlation to the plasma membrane marker 5'-nucleotidase. These results suggest the existence of inhibitory opioid receptors (kappa- and delta-receptors) on excitatory neurons in the intestinal neuronal pathway, which activates the canine pylorus.