Immunocyochemical labeling was applied to follow the developmental changes in the calcium‐binding proteins parvalbumin (PV), calbindin D28k (CaB), and calretinin (CaR) during fetal and infant development of Macaca monkey dorsal lateral geniculate nucleus (LGN). For all three proteins, LGN cell body and retinal ganglion cell (RGC) axon labeling patterns changed temporally and spatially over development, and many of these were LGN laminar specific. CaR+ and CaB+ cells were present at the youngest age studied, fetal day 55 (F55). After lamination of the LGN occurred between F90 and F115, CaR+ and CaB+ neurons were specific markers for the S, intercalated, and interlaminar layers. Double label immunocytochemistry showed that all CaR+ cells contained CaB, and none contained GABA. CaR+ cell bodies decreased in number soon after birth so that adult LGN contained only a very small number of CaR+ cells. These patterns and cell counts indicated that a downregulation of CaR had occurred in the CaB+ population. Although CaB+ cell density in S and interlaminar zones declined in the adult, cell counts indicated that this is due to dilution of a stable population into a much larger nucleus during development. PV+ cells appeared at F85 only within the putative magnocellular (M) and parvocellular (P) layers, and PV remained a marker for these layers throughout development. Fetal PV cells also contained GABA, indicating that they were LGN interneurons. After birth, GABA−/PV+ cell numbers increased dramatically throughout the whole nucleus so that by the end of the first year, P and M layers were filled with PV+ cells. Their number and size indicated that these were the LGN projection neurons. Beginning at F66, bundles of PV+ axons occupied the anterior‐middle LGN and filled the optic tract. Up to F101, PV+ synaptic terminals were restricted to P layers, but after F132 labeling in M layers was heavier than in P layers. Axonal labeling for CaR began at F125. Prenatally CaR+ terminals were present mainly in P layers, whereas by postnatal 9 weeks labeling in M layers much exceeded P layers. Axonal labeling for CaB was present at F132, but CaB+ terminals were observed only after birth with labeling always heavier in M than P layers. By postnatal 9 weeks, PV, CaR, and CaB were colocalized in the same axons and terminals. These experiments indicated that during development and in the adult LGN, both CaR and CaB were markers for the LGN neurons in the S and intercalated pathway. CaR was present transiently while CaB persisted into adulthood. PV was a M and P layer marker first for interneurons and later for projection cells. The complex temporal developmental patterns found in this study suggested that viewing PV, CaB, and CaR simply as calcium‐buffering proteins severely underestimates their functional roles during visual system maturation. © 1996 John Wiley & Sons, Inc.

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The effect of ANG II on mucosal ion transport and localization of ANG type 1 receptor (AT(1)R) in the guinea pig distal colon was investigated. Submucosal/mucosal segments were mounted in Ussing flux chambers, and short-circuit current (I(sc)) was measured as an index of ion transport. Serosal addition of ANG II produced a concentration-dependent (10(-9)-10(-5) M) increase in I(sc). The maximal response was observed at 10(-6) M; the increase in I(sc) was 164.4 +/- 11.8 microA/cm(2). The ANG II (10(-6) M)-evoked response was mainly due to Cl(-) secretion. Tetrodotoxin, atropine, the neurokinin type 1 receptor antagonist FK-888, and piroxicam significantly reduced the ANG II (10(-6) M)-evoked response to 28, 45, 58, and 16% of control, respectively. Pretreatment with prostaglandin E(2) (10(-5) M) resulted in a threefold increase in the ANG II-evoked response. The AT(1)R antagonist FR-130739 completely blocked ANG II (10(-6) M)-evoked responses, whereas the ANG type 2 receptor antagonist PD-123319 had no effect. Localization of AT(1)R was determined by immunohistochemistry. In the immunohistochemical study, AT(1)R-immunopositive cells were distributed clearly in enteric nerves and moderately in surface epithelial cells. These results suggest that ANG II-evoked electrogenic Cl(-) secretion may involve submucosal cholinergic and tachykinergic neurons and prostanoid synthesis pathways through AT(1)R on the submucosal plexus and surface epithelial cells in guinea pig distal colon.

The ATP-sensitive potassium channel (KATP channel) is an essential ion channel involved in glucose-induced insulin secretion. The KATP channel is composed of an inwardly rectifying potassium channel, Kir6.2, and the sulfonylurea receptor (SUR 1); in the pancreas it is reported to be shared by all endocrine cell types. A previous study by our research group showed that Kir 6.2-knockout mice lacked KATP channel activities and failed to secrete insulin in response to glucose, but displayed normal blood glucose levels and only mild impairment in glucose tolerance at younger ages. In some aged knockout mice, however, obesity and hyperglycemia were recognizable. The present study aimed to reveal morphological changes in pancreatic islets of Kir 6.2-knockout mice throughout life. At birth, there were no significant differences in the islet cell arrangement between the knockout mice and controls. At 14 postnatal weeks glucagon cells appeared in the central parts of islets, and this image became more pronounced with aging. In animals older than 50 weeks insulin cells decreased in numbers and intensity of insulin immunoreactivity; most islets in 70- and 80-week-old mice were predominantly composed of glucagon cells and peptide YY (PYY)-containing cells. Staining of serial sections and double staining of single sections from these old mice demonstrated the frequent coexpression of glucagon and PYY, which is a phenotype for the earliest progenitor cells of pancreatic endocrine cells. These findings suggest that the KATP channel is important for insulin cell survival and also regulates the differentiation of islet cells.

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