Adenosine A2 receptor-mediated excitatory actions on the nervous system.

Pituitary adenylate cyclase-activating peptide stimulates neurite growth in PC12 cells

1. The effect of calcitonin gene-related peptide (CGRP) on [3H]-acetylcholine ([3H]-ACh) release from motor nerve endings and its interaction with presynaptic facilitatory A2a-adenosine and nicotinic acetylcholine receptors was studied on rat phrenic nerve-hemidiaphragm preparations loaded with [3H]-choline. 2. CGRP (100-400 nM) increased electrically evoked [3H]-ACh release from phrenic nerve endings in a concentration-dependent manner. 3. The magnitude of CGRP excitation increased with the increase of the stimulation pulse duration from 40 microseconds to 1 ms, keeping the frequency, the amplitude and the train length constants. With 1 ms pulses, the evoked [3H]-ACh release was more intense than with 40 microseconds pulse duration. 4. Both the nicotinic acetylcholine receptor agonist, 1,1-dimethyl-4-phenylpiperazinium, and the A2a adenosine receptor agonist, CGS 21680C, increased evoked [3H]-ACh release, but only CGS 21680C potentiated the facilitatory effect of CGRP. This potentiation was prevented by the A2a adenosine receptor antagonist, PD 115,199. 5. Adenosine deaminase prevented the excitatory effect of CGRP (400 nM) on [3H]-ACh release. This effect was reversed by the non-hydrolysable A2a-adenosine receptor agonist, CGS 21680C. 6. The nicotinic antagonist, tubocurarine, did not significantly change, whereas the A2-adenosine receptor antagonist, PD 115,199, blocked the CGRP facilitation. The A1-adenosine receptor antagonist, 1,3-dipropyl-8-cyclopentylxanthine, potentiated the CGRP excitatory effect. 7. The results suggest that the facilitatory effect of CGRP on evoked [3H]-ACh release from rat phrenic motor nerve endings depends on the presence of endogenous adenosine which tonically activates A2a-adenosine receptors.(ABSTRACT TRUNCATED AT 250 WORDS)

Potentiation by tonic A2a-adenosine receptor activation of CGRP-facilitated [3H]-ACh release from rat motor nerve endings

Brain-derived neurotrophic factor enhances the contraction of intestinal muscle strips induced by SP and CGRP in mice.

Neuroligands evoke calcium signaling in cultured myenteric neurons.

The effects of calcitonin gene-related peptide (CGRP) on acetylcholine (ACh) release from myenteric plexus neurons in primary culture were investigated. CGRP (10(-12) to 10(-6) M) produced a dose-dependent increase in [3H]ACh release. The ACh release caused by CGRP was significantly inhibited (74 +/- 24%) by preincubation with dideoxyadenosine but was increased more than threefold by preincubation with theophylline. Incubation of myenteric plexus neurons with CGRP (10(-8) M) in the presence of diltiazem (10(-5) M) or in a calcium-free medium markedly reduced [3H]ACh release. CGRP potentiated [3H]ACh release stimulated by potassium or substance P but not by cholecystokinin octapeptide or forskolin. The results demonstrate that CGRP cause release of ACh from guinea pig myenteric plexus neurons and suggest that the peptide acts through an adenosine 3',5'-cyclic monophosphate-dependent mechanism that involves neuronal calcium channels.

S. Jaffer

Papers

Stimulation of acetylcholine release in myenteric plexus by calcitonin gene-related peptide.