title: Receptor-mediated release of inositol phosphates in the cochlear and vestibular sensory epithelia of the rat.
abstract: Various neurotransmitters, hormones and other modulators involved in intercellular 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 purinergic receptors. However, nothing is known about the InsP3 second messenger system in the vestibule. In this study, the receptor-mediated release of inositol phosphates (InsPs) in the vestibular sensory epithelia was compared to that in the cochlear sensory epithelia of Fischer-344 rats. After preincubation of the isolated intact tissues with myo-[3H]inositol, stimulation with the cholinergic agonist carbamylcholine or the P2 purinergic agonist ATP-gamma-S resulted in a concentration-dependent increase in the formation of [3H]InsPs in both epithelia. Similarly, the muscarinic cholinergic agonist muscarine enhanced InsPs release in both organs, while the nicotinic cholinergic agonist dimethylphenylpiperadinium (DMPP) was ineffective. The muscarinic cholinergic antagonist atropine completely suppressed the InsPs release induced by carbamylcholine, while the nicotinic cholinergic antagonist mecamylamine was ineffective. Potassium depolarization did not alter unstimulated or carbamylcholine-stimulated release of InsPs in either organ. In both tissues, the P2 purinergic agonist alpha,beta-methylene ATP also increased InsPs release, but the P1 purinergic agonist adenosine did 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 the InsP3 second messenger system in the vestibular sensory epithelia.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Kresge Hearing Research Institute, University of Michigan, Ann Arbor 48109-0506.
authors.forename: K
authors.initials: K
authors.lastname: Ogawa
authors.forename: J
authors.initials: J
authors.lastname: Schacht
mesh_terms: D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology; D003051:Cochlea / Q000187:drug effects / Q000378:metabolism*; D004848:Epithelium / Q000378:metabolism; D006868:Hydrolysis; D007294:Inositol / Q000494:pharmacology; D007295:Inositol Phosphates / Q000378:metabolism*; D008297:Male; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D011916:Rats, Inbred F344; D011950:Receptors, Cholinergic / Q000187:drug effects / Q000502:physiology*; D011983:Receptors, Purinergic / Q000187:drug effects / Q000502:physiology*; D015290:Second Messenger Systems; D014722:Vestibule, Labyrinth / Q000187:drug effects / Q000378:metabolism*
chemical_list: D007295:Inositol Phosphates; D011950:Receptors, Cholinergic; D011983:Receptors, Purinergic; C022571:adenosine 5'-O-(3-thiotriphosphate); D007294:Inositol; D001285:Atropine; D000255:Adenosine Triphosphate; D002217:Carbachol; D011188:Potassium