Developmental changes in carbachol-stimulated inositolphosphate release in pigmented rat retina.
Carbachol-stimulated release of inositolphosphates (IP) was studied in the whole retina from Long-Evans rats of different ages (day 5, 10, 15, 20, adult) following in vitro incorporation of [3H]myo-inositol. Unlike the albino rat retina, the pigmented retina was highly light-sensitive, making it necessary to dark adapt the animals and perform retinal dissections under low illumination to prevent light-induced IP release. Retinae from postnatal day 10 rats showed the highest amount of carbachol-stimulated IP released. This response to carbachol decreased with age until postnatal day 20 when it reached adult levels. The pigmented rat retina showed a sharp fall in the degree of carbachol (1 mM)-stimulated IP released at the time of eye-opening (450% above basal in retinae from 10 day old animals, as compared to 230% above basal in 15 day old retinae). Basal release of IP was not altered in the retina during development. Muscarinic cholinergic receptor density was, however, found to increase 5 fold with age, reaching adult levels by PND 20. Retinal weight and protein per retina also increased (four fold) from day 5 to adult; however, the in vitro incorporation of [3H]myo-inositol into phosphoinositides (calculated as per mg protein) did not change during development. Thus, in animals prior to eye opening, a much higher proportion of phosphoinositides appears to be hydrolyzed upon muscarinic receptor stimulation. During retinal development a change in sensitivity to the agonist-sensitive pool(s) of phosphoinositides may occur and/or there may be alterations in the efficacy of receptor coupling to the second messenger system resulting in the disassociation observed between the drastic increase in receptor number and the apparent decrease in receptor-stimulated release of IP.
Tandon
P
P
Neurotoxicology Div. (MD-74B), US Environmental Protection Agency, Research Triangle Park, NC.
Pope
C
C
Padilla
S
S
Tilson
H A
HA
Harry
G J
GJ
D000375:Aging / Q000502:physiology*; D000818:Animals; D002217:Carbachol / Q000494:pharmacology*; D003623:Dark Adaptation; D005136:Eye Proteins / Q000378:metabolism; D005260:Female; D007295:Inositol Phosphates / Q000378:metabolism*; D008297:Male; D010743:Phospholipids / Q000378:metabolism; D010858:Pigmentation; D051381:Rats; D011916:Rats, Inbred F344; D011976:Receptors, Muscarinic / Q000378:metabolism; D012160:Retina / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism*
D005136:Eye Proteins; D007295:Inositol Phosphates; D010743:Phospholipids; D011976:Receptors, Muscarinic; D002217:Carbachol