RECEPTOR-MEDIATED RELEASE OF INOSITOL PHOSPHATES IN THE COCHLEAR AND VESTIBULAR SENSORY EPITHELIA OF THE RAT

Various neurotransmitters, hormones and other modulators involved in i ntercellular communication exert their biological action at receptors coupled to phospholipase C (PLC). This enzyme catalyzes the hydrolysis of phosphatidylinositol 4,5-bisphosphate (PtdInsP2) to inositol 1,4,5 -trisphosphate (InsP3) and 1,2-diacylglycerol (DG) which act as second messengers. In the organ of Corti of the guinea pig, the InsP3 second messenger system is linked to muscarinic cholinergic and P2y purinerg ic receptors. However, nothing is known about the the InsP3 second mes senger system in the vestibule. In this study, the receptor-mediated r elease of inositol phosphates (InsPs) in the vestibular sensory epithe lia was compared to that in the cochlear sensory epithelia of Fischer- 344 rats. After preincubation of the isolated intact tissues with myo- [H-3]inositol, stimulation with the cholinergic agonist carbamylcholin e or the P2 purinergic agonist ATP-gamma-S resulted in a concentration -dependent increase in the formation of [H-3]InsPs in both epithelia. Similarly, the muscarinic cholinergic agonist muscarine enhanced InsPs release in both organs, while the nicotinic cholinergic agonist dimet hylphenylpiperadinium (DMPP) was ineffective. The muscarinic cholinerg ic antagonist atropine completely suppressed the InsPs release induced by carbamylcholine, while the nicotinic cholinergic antagonist mecamy lamine was ineffective. Potassium depolarization did not alter unstimu lated or carbamylcholine-stimulated release of InsPs in either organ. In both tissues, the P2 purinergic agonist alpha,beta-methylene ATP al so increased InsPs release, but the P1 purinergic agonist adenosine di d not. These results extend our previous observations in the organ of Corti of the guinea pig to the rat and suggest a similar control of th e InsP3 second messenger system in the vestibular sensory epithelia. I n contrast to the cochlear sensory epithelia, atropine also significan tly suppressed unstimulated InsPs release in the vestibular sensory ep ithelia. This suggests that the physiological mechanisms of the effere nt nervous systems involving InsP3 second messenger system might be di fferent in vestibular versus cochlear sensory epithelia.