Both ATP and the peptide VIP are inhibitory neurotransmitters in guinea‐pig ileum circular muscle.

Abstract

SUMMARY1. Intracellular membrane potential recordings were made from circular smooth muscle cells of the guinea-pig ileum in the presence of atropine (1 #M) and nifedipine (01I,tM) at 30 'C.2. Perfusion with adenosine triphospate (ATP, 100 /LM) and vasoactive intestinal peptide (VIP, 2 ,SM) resulted in membrane hyperpolarizations of 6-4 + 0 3 and 6'8 + 03 mV, respectively. Picospritzes of ATP (10 mm in pipette) and VIP (100 tim in pipette) resulted in membrane hyperpolarizations of 6-9 + 04 and 6-3 + 04 mV, respectively.3. The ATP-induced hyperpolarizations were antagonized by ac, ,3-methylene ATP desensitization (100 ,tM for 30 min) and the ATP antagonist Reactive Blue 2 (200 /tM), but were unaffected by the VIP antagonist VIP 10-28 (1 JiM).4. The VIP-induced hyperpolarizations were antagonized by VIP 10-28, but unaffected by a, ,-methylene ATP desensitization and Reactive Blue 2.5. A single pulse of transmural nerve stimulation (2 ms, 15 mA) resulted in an inhibitory junction potential (IJP) that reached a maximal amplitude of 12-9 + 0-5 mV at 378 + 20 ms from the stimulus. This fast IJP was abolished by apamin (2 /zM) or tetrodotoxin (1 pM), antagonized by a, fl-methylene ATP desensitization or Reactive Blue 2, but unaffected by VIP 10-28.6. In the presence of apamin (1 fM), four pulses of transmural stimulation (2 ms, 20 Hz, 15 mA) resulted in an IJP that reached a maximal amplitude of 4-8 + 0-2 mV at 14 + 0-1 s from the stimulus. This slow IJP was antagonized by tetrodotoxin (1 /LM) or VIP 10-28 (1 /bM), augmented by Reactive Blue 2 (200 jm), and unaffected by ax, ,J-methylene ATP desensitization.7. These findings provide evidence that both ATP and VIP are inhibitory neurotransmitters in the circular muscle layer of the ileum and that ATP may be the neurotransmitter responsible for the fast IJP and VIP the neurotransmitter responsible for the slow IJP.MS 9154

Neural modulation of the cyclic electrical and mechanical activity in the rat colonic circular muscle: putative role of ATP and NO

“…IJPs recorded from the rat colon showed two phases: a sharp decrease of the membrane potential (fast component) followed by a sustained hyperpolarization (slow component). This biphasic IJP is similar to those described in other preparations such as mouse colon (Shuttleworth et al, 1997), mouse ileum (Ward et al, 1994), guinea-pig taenia caeci (Bridgewater et al, 1995), guinea-pig ileum (Crist et al, 1992), human colon (Keef et al, 1993) and human jejunum (Stark et al, 1993), whereas a monophasic IJP has been recorded from the pig (Borderies et al, 1997) and dog (Stark et al, 1993) ileum. The presence of two components in the IJP may suggest a cotransmission.…”

“…However, it has become evident that IJPs may often show two phases, a fast and a slow hyperpolarization. Thus, this pro®le has been described for the IJP elicited by EFS of mouse colon (Shuttleworth et al, 1997), mouse ileum (Ward et al, 1994), guinea-pig taenia caeci (Bridgewater et al, 1995), guinea-pig ileum (Crist et al, 1992), human colon (Keef et al, 1993) and human jejunum (Stark et al, 1993). This biphasic shape of the IJP may suggest the release of more than one neurotransmitter.…”

Regulation of Guinea pig intestinal peristalsis by endogenous endothelin acting at ETB receptors

“…26,29,30,33,34 The antiperistaltic action of STX-6c was analyzed with respect to the possibility that this ET B receptor agonist depresses peristalsis via activation of inhibitory motor neurons, which in the guinea pig intestine relax the muscle primarily via release of NO, ATP, vasoactive intestinal polypeptide, and/or pituitary adenylate cyclaseactivating peptide. [35][36][37][38] However, peristaltic motor inhibition caused by STX-6c remained unaltered by an effective concentration (300 µmol/L) of the NO synthase inhibitor L-NAME, 25,39 which is in line with a lack of NO involvement in ET-induced suppression of intestinal muscle contractility. 11,13 Effective concentrations of the P2X purinoceptor antagonist PPADS, which antagonizes the antiperistaltic action of endogenously released ATP, 27,40 and of the opioid receptor antagonist naloxone 26 were likewise unable to prevent STX-6c from inhibiting peristalsis.…”

Purinergic receptors and synaptic transmission in enteric neurons

“…All motor neurons have S-type properties and, like the interneurons, they can differ in their level of excitability [12]. In the myenteric plexus, inhibitory motor neurons to the circular muscle are immunoreactive for NOS and VIP and use ATP as a coneurotransmitter [1,6,18]. In the submucous plexus, there are two types of excitatory secretomotor neurons going to the epithelium and at least one type of vasodilator neuron to the submucous arterioles.…”