Identification of muscarinic receptor subtypes involved in catecholamine secretion in adrenal medullary chromaffin cells by genetic deletion

Activation of muscarinic receptors

Activation of muscarinic receptors

Muscarinic M&sub1;, M&sub4; and M₅ receptors were immunologically detected in mouse chromaffin cells, and these receptors disappeared after the appropriate gene deletion. Mouse cells secreted catecholamines in response to muscarinic agonists, angiotensin II and a decrease in external pH. Genetic deletion of M&sub1;, but not M&sub3;, M&sub4; or M₅, receptors in mice abolished secretion in response to muscarine, but not to other stimuli. The muscarine-induced secretion was suppressed by MT7, a snake peptide toxin specific for M&sub1; receptors. Similarly, muscarine failed to induce an inward current in the presence of MT7 in mouse and rat chromaffin cells. The binding affinity of VU0255035 for the inhibition of muscarine-induced currents agreed with that for the M&sub1; receptor. Conclusions and implications: Based upon the effects of genetic deletion of muscarinic receptors and MT7, it is concluded that the M&sub1; receptor alone is responsible for muscarine-induced catecholamine secretion.