Pituitary adenylate cyclase-activating polypeptide (PACAP) is a widespread neuropeptide with a diverse array of biological functions. Not surprisingly, the lack of endogenous PACAP therefore results in a variety of abnormalities. One of the important effects of PACAP is its neuroprotective and general cytoprotective role. PACAP protects neurons and other tissues against ischemic, toxic, and traumatic lesions. Data obtained from PACAP-deficient mice provide evidence that endogenous PACAP also has protective functions. Mice lacking PACAP are more vulnerable to different in vitro and in vivo insults. The present review summarizes data on the increased sensitivity of PACAP-deficient mice against harmful stimuli. Mice lacking PACAP respond with a higher degree of injury in cerebral ischemia, autoimmune encephalomyelitis, and axonal lesion. Retinal ischemic and excitotoxic injuries also produce increased cell loss in PACAP-deficient mice. In peripheral organs, kidney cell cultures from PACAP-deficient mice are more sensitive to oxidative stress and in vitro hypoxia. In vivo, PACAP-deficient mice have a negative histological outcome and altered cytokine response in kidney and small intestine ischemia/reperfusion injury. Large intestinal inflammation, toxic lesion of the pancreas, and doxorubicin-induced cardiomyopathy are also more severe with a lack of endogenous PACAP. Finally, an increased inflammatory response has been described in subacute endotoxin-induced airway inflammation and in an oxazolone-induced allergic contact dermatitis model. In summary, lack of endogenous PACAP leads to higher vulnerability in a number of injuries in the nervous system and peripheral organs, supporting the hypothesis that PACAP is part of the endogenous cytoprotective machinery.

We studied the responses of rod photoreceptors that were elicited with light flashes or sinusoidally modulated light by using intracellular recording. Dark-adapted Xenopus rod photoreceptors responded to sinusoidally modulated green lights at temporal frequencies between 1 Hz and 4 Hz. In normal Ringer's solution, 57% of the rods tested could follow red lights that were matched for equal rod absorbance to frequencies >5 Hz, indicating an input from red-sensitive cones. Quinpirole (10 μM), a D2 dopamine agonist, increased rod-cone coupling, whereas spiperone (5 μM), a selective D2 antagonist, completely suppressed it. D1 dopamine ligands were without effect. Neurobiotin that was injected into single rods diffused into neighboring rods and cones in quinpirole-treated retinas but only diffused into rods in spiperone-treated retinas. A subpopulation of rods (ca. 10% total rods) received a very strong cone input, which quickened the kinetics of their responses to red flashes and greatly increased the bandpass of their responses to sinusoidally modulated light. Based on electron microscopic examination, which showed that rod-rod and cone-cone gap junctions are common, whereas rod-cone junctions are relatively rare, we postulate that cone signals enter the rod network through a minority of rods with strong cone connections, from which the cone signal is further distributed in the rod network. A semiquantitative model of coupling, based on measures of gapjunction size and distribution and estimates of their conductance and open times, provides support for this assumption. The same network would permit rod signals to reach cones. Keywords gap junction; photoreceptor; retina; neuromodulation When rod photoreceptors are fully dark-adapted, they respond reliably to the absorbance of a single quantum of light (Yau et al., 1977). Rods continue to function when they are desensitized by background lights (Fain, 1976) or by prior exposure to light, and, in those circumstances, the effective stimuli for rods can be sufficiently bright to also activate cone photoreceptors, allowing for the possibility of interactions between rod signals and cone signals. (Raviola and Gilula, 1973), and functional rod-cone coupling in primate retina has been reported (Schneeweis and Schnapf, 1995).The main experimental question of the present study is whether the conductances of photoreceptor gap junctions are subject to neuromodulation. We focus on the intrinsic retinal neurochemical, dopamine (Haggendal and Malmfors, 1965), which is known to modulate the gap-junctional conductance of retinal second-order neurons (Piccolino et al., 1984) and to augment information flow in cone circuits while suppressing that in rod circuits (Witkovsky and Dearry, 1991). Photoreceptors have dopamine receptors of the D2/D4 subtypes (Cohen et al., 1992;Muresan and Besharse, 1993). In the present study, we found that a D2 dopamine agonist, but not a D1 agonist, increases rod-cone coupling in the Xenopus retina, resulting in altered rod light-evoked response k...

The length of the uterine cervix, measured by transvaginal sonography, is a better predictor of the risk of Cesarean section than the Bishop score after induction of labor for medical reasons. In women with an unfavorable Bishop score, a cervical length of < 26 mm is associated with a lower risk of Cesarean section and a shorter duration of labor.

We investigated the cellular localization in the salamander retina of one of the somatostatin [or somatotropin release-inhibiting factor (SRIF)] receptors, sst(2A), and studied the modulatory action of SRIF on voltage-gated K(+) and Ca(2+) currents in rod and cone photoreceptors. SRIF immunostaining was observed in widely spaced amacrine cells, whose perikarya are at the border of the inner nuclear layer and inner plexiform layer. sst(2A) immunostaining was seen in the inner segments and terminals of rod and cone photoreceptors. Additional sst(2A) immunoreactivity was expressed by presumed bipolar and amacrine cells. SRIF, at concentrations of 100-500 nM, enhanced a delayed outwardly rectifying K(+) current (I(K)) in both rod and cone photoreceptors. SRIF action was blocked in cells pretreated with pertussis toxin (PTX) and was substantially reduced by intracellular GDP(beta)S. Voltage-gated L-type Ca(2+) currents in rods and cones were differently modulated by SRIF. SRIF reduced Ca(2+) current in rods by 33% but increased it in cones by 40%, on average. Both effects were mediated via G-protein activation and blocked by PTX. Ca(2+)-imaging experiments supported these results by showing that 500 nM SRIF reduced a K(+)-induced increase in intracellular Ca(2+) in rod photoreceptor terminals but increased it in those of cones. Our results suggest that SRIF may play a role in the regulation of glutamate transmitter release from photoreceptors via modulation of voltage-gated K(+) and Ca(2+) currents.

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