EVIDENCE THAT ENHANCEMENT OF CHOLINERGIC TONE INCREASES BASAL PLASMA-LEVELS OF CALCITONIN-GENE-RELATED PEPTIDE IN NORMAL MAN

To investigate the influence of the cholinergic system on the modulati on of the circulating levels of calcitonin gene-related peptide (CGRP) under basal conditions in normal man, the effects of an acetylcholine sterase inhibitor, pyridostigmine bromide, and a muscarinic receptor b locker, pirenzepine, were studied in 16 normal subjects (8 females and 8 males). Pyridostigmine (120 mg, orally) induced a significant (P < 0.01) rise in basal plasma CGRP, while it reduced systolic and diastol ic blood pressure. In all subjects, pirenzepine (0.6 mg/kg, iv bolus) was unable to modify the basal CGRP level. In conclusion, a pharmacolo gically induced enhancement of cholinergic tone resulted in an increas e in CGRP, whereas muscarinic receptor blockade had no effect on CGRP levels or blood pressure. Therefore, the cholinergic system seems to b e involved in the control of CGRP release in man, acting as a positive modulator. However, the available data do not indicate that there is a tonic cholinergic tone responsible for CGRP secretion under physiolo gical conditions.