Receptors on Rat Motoneurons

At the rat motor endplate, pre-synaptic facilitatory adenosine A 2A and muscarinic M 1 receptors are mutually exclusive. We investigated whether these receptors share a common intracellular signalling pathway. Suppression of McN-A-343-induced M 1 facilitation of [ 3 H]ACh release was partially recovered when CGS21680C (an A 2A agonist) was combined with the cyclic AMP antagonist Rp-cAMPS. Forskolin, rolipram and 8-bromo-cyclic AMP mimicked CGS21680C blockade of M 1 facilitation. Both Rp-cAMPs and nifedipine reduced augmentation of [ 3 H]ACh release by McN-A-343 and CGS21680C. Activation of M 1 and A 2A receptors enhanced Ca 2+ recruitment through nifedipine-sensitive channels. Nifedipine inhibition revealed by McN-A-343 was prevented by chelerythrine (a PKC inhibitor) and Rp-cAMPS, suggesting that Ca v 1 (L-type) channels phosphorylation by PKA and PKC is required. Rp-cAMPS inhibited [ 3 H]ACh release in the presence of phorbol 12-myristate 13-acetate, but PKC inhibition by chelerythrine had no effect on release in the presence of 8-bromo-cyclic AMP. This suggests that the Received: May 19, 2005 Accepted after revision: July 21, 2005 Paulo Correia-de-Sá, MD, PhD Laboratório de Farmacologia, Unidade Multidisciplinar de Investigação Biomédica Instituto de Ciências Biomédicas de Abel Salazar, Universidade do Porto L. Prof. Abel Salazar, 2, PT–4099-003 Porto (Portugal) Tel. +351 22 2062243, Fax +351 22 2062252, E-Mail [email protected] © 2005 S. Karger AG, Basel 1424–862X/05/0145–0262$22.00/0 Accessible online at: