Role of α₂‐adrenoceptors in the sympathetic inhibition of motility reflexes of guinea‐pig ileum

Abstract

1. Sympathetic regulation of the motility of guinea-pig ileum was investigated using mesenteric nerve (MN) stimulation to inhibit motility reflexes, in vitro.2. Transmural electrical stimulation (5 Hz, 1 s) in intact intestinal segments, or inflation of a balloon against the mucosa in opened segments, evoked contractions of the circular and longitudinal muscles oral to the stimulus.3. MN stimulation (10 Hz, 5 s) usually abolished contractions of the longitudinal and circular muscles evoked by either electrical or mechanical stimuli.4. The inhibition was mimicked by UK14,304 (70-100 nM) and abolished by idazoxan (100 nM), revealing an enhancement of circular muscle contractions. There was no evidence for a 2 -receptors on the muscle, suggesting sympathetic inhibition was via the myenteric plexus.5. Possible sites of action of noradrenaline released from sympathetic nerves were investigated using intracellular recordings from the circular muscle in a multichambered organ bath.6. When in the stimulation chamber, UK14,304 depressed (by 50 %) excitatory junction potentials (EJPs) recorded oral to a distension stimulus, but did not affect inhibitory junction potentials (IJPs) recorded anal to the stimulus. When added to a chamber between the stimulus and recording chambers, UK14,304 depressed EJPs by 40 %, but did not alter IJPs. When in the recording chamber, UK14,304 depressed EJPs by 20 %, but had no effect on IJPs. IJPs were inhibited, however, when UK14,304 was applied to the whole bath.7. It is concluded that sympathetic activity inhibits intestinal motility mainly via a 2 -adrenoceptors on ascending interneurons and intrinsic sensory neurons of the orally directed reflex pathway.

Enteric Glia Are Targets of the Sympathetic Innervation of the Myenteric Plexus in the Guinea Pig Distal Colon

“…In the myenteric plexus of the gastrointestinal tract, sympathetic stimulation releases NE and the cotransmitter ATP (Al-Humayyd and White, 1985). Although NE is thought to inhibit enteric neurons via presynaptic adrenergic receptors (Hirst and McKirdy, 1974;Tack and Wood, 1992;Spencer et al, 1999;Stebbing et al, 2001), the role of sympathetic ATP release is less clearly defined (Venkova and Krier, 1993;Kadowaki et al, 2003). Our results suggest that sympathetic varicosities release ATP to activate enteric glia.…”

Fine structural survey of tyrosine hydroxylase immunoreactive terminals in the myenteric ganglion of the rat duodenum

“…About 16% of axosomatic terminals showed TH-like immunoreactivity. Acetylcholine excites, but noradrenaline inhibits neuronal activity of the myenteric ganglion neurons (Nishi and North, 1973;Gabella, 1994;Gershon et al, 1994;Stebbing et al, 2001). Thus it is likely that the myenteric ganglion neurons in the duodenum receive direct noradrenergic inhibitory projections in addition to projection from intrinsic enteric neurons and extrinsic cholinergic excitatory projections.…”

Dynamics of fast synaptic excitation during trains of stimulation in myenteric neurons of guinea-pig ileum

“…α 2 -adrenoceptors are localized to cholinergic neurons and these receptors mediate inhibition of acetylcholine release onto myenteric S neurons (Stebbing et al, 2001;Scheibner et al, 2002). Opioid receptors are expressed in cell bodies and processes of myenteric neurons and activation of opioid receptors inhibits the electrically evoked release of ACh (Sternini, 2001).…”