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001-es BibID:	BIBFORM039245
Első szerző:	Ács Géza (traumatológus)
Cím:	Differential activation and desensitization of sensory neurons by resiniferatoxin / Acs, G., Biro, T., Acs, P., Modarres, S., Blumberg, P. M.
Dátum:	1997
ISSN:	0270-6474
Megjegyzések:	Recently, with use of rat dorsal root ganglion (DRG) neurons we have been able to dissociate the binding affinities of vanilloids from their potencies to induce Ca-45 uptake, which suggests the existence of distinct classes of the vanilloid receptor (Acs et al., 1996). In the present study, we have demonstrated that the ultrapotent capsaicin analog resiniferatoxin (RTX) desensitized rat DRG neurons to the subsequent induction of Ca-45 uptake by capsaicin and RTX with affinity and cooperativity similar to that found for [H-3]RTX binding, contrasting with a similar to 10-fold weaker potency and lack of cooperativity to induce Ca-45 uptake. Likewise, the competitive antagonist capsazepine inhibited RTX-induced desensitization with potency similar to that for inhibition of specific [H-3]RTX binding, whereas the potency of capsazepine was similar to 10-fold higher for inhibiting RTX-induced Ca-45 uptake. Finally, the noncompetitive antagonist ruthenium red inhibited both the RTX-induced desensitization and Ca-45 uptake but showed similar to 60-fold selectivity for inhibiting RTX-induced desensitization. The RTX-induced desensitization was not associated with loss of specific [H-3]RTX binding, suggesting lack of gross cell toxicity. In contrast to RTX, capsaicin caused desensitization with a potency corresponding to that for Ca-45 uptake and did so in a noncooperative manner. Unlike the RTX-induced desensitization, the desensitization by capsaicin was blocked by ruthenium red only at doses that blocked Ca-45 uptake and depended on external calcium, Our findings provide further support for the existence of vanilloid receptor subtypes on DRG neurons with distinct pharmacology and distinct patterns of desensitization.
Tárgyszavak:	Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
Megjelenés:	Journal of Neuroscience. - 17 : 14 (1997), p. 5622-5628. -
További szerzők:	Bíró Tamás (1968-) (élettanász) Ács Péter Modarres, Shayan Blumberg, Peter M.
Internet cím:	elektronikus változat Intézményi repozitóriumban (DEA) tárolt változat
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001-es BibID:	BIBFORM039246
Első szerző:	Bíró Tamás (élettanász)
Cím:	Recent advances in understanding of vanilloid receptors : a therapeutic target for treatment of pain and inflammation in skin / Biro, T., Acs, G., Acs, P., Modarres, S., Blumberg, P. M.
Dátum:	1997
Megjegyzések:	C-fiber sensory afferent neurons, which contain neuropeptides such as calcitonin-gene related peptide and substance P, mediate a wide variety of physiologic responses, including chemogenic pain, thermoregulation, and neurogenic inflammation. Capsaicin, the pungent constituent in red pepper, functions to activate and then, at higher doses and longer times, desensitize this class of neurons, This latter response provides the basis for the therapeutic application of capsaicin, A major advance in the field has been the identification of resiniferatoxin, a phorbol-related diterpene, as an analog of capsaicin that is ultrapotent but with differential selectivity, In particular, resiniferatoxin is only similar in potency for induction of pain but is much more effective for desensitization, Structure-activity analysis in whole animal experiments provides further evidence for dissociation of biologic endpoints, strongly arguing for the existence of vanilloid receptor subclasses, Using resiniferatoxin, we have been able to define specific, high-affinity receptors for capsaicin both in animal models such as rats and in man, Of great importance, the pharmacologic characterization in cultured dorsal root ganglion cells of the high-affinity resiniferatoxin-binding site and of tile physiologic response believed to be directly coupled to the receptor, viz, calcium uptake, differed in structure-activity and in cooperativity. We conclude that multiple high-affinity vanilloid receptor subclasses mediate vanilloid response; moreover, the resiniferatoxin-selective subclass of vanilloid receptors is not the voltage-independent, cation-nonselective ion channel as previously believed, Optimization of ligands for the individual vanilloid receptor subclasses should revolutionize this therapeutic area.
Tárgyszavak:	Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
Megjelenés:	Journal of Investigative Dermatology Symposium Proceedings. - 2 : 1 (1997), p. 56-60. -
További szerzők:	Ács Géza (1939-) (traumatológus) Ács Péter Modarres, Shayan Blumberg, Peter M.
Internet cím:	elektronikus változat Intézményi repozitóriumban (DEA) tárolt változat
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001-es BibID:	BIBFORM039266
Első szerző:	Bíró Tamás (élettanász)
Cím:	Characterization of functional vanilloid receptors expressed by mast cells / Biro, T., Maurer, M., Modarres, S., Lewin, N. E., Brodie, C., Acs, G., Acs, P., Paus, R., Blumberg, P. M.
Dátum:	1998
ISSN:	0006-4971
Megjegyzések:	Capsaicin and its ultrapotent analog resiniferatoxin (RTX) act through specific vanilloid receptors on sensory neurons. The C-type receptor is coupled to Ca-45 uptake, whereas the R-type is detectable by [H-3]RTX binding. We describe here specific vanilloid responses in murine mast cells (MCs). In the MC lines and in bone marrow-derived mast cells. capsaicin and RTX induced Ca-45 uptake similarly to that observed for cultured rat dorsal root ganglion neurons (DRGs). This response was antagonized by the antagonists capsazepine and ruthenium red. As in DRGs, pretreatment of MCs with capsaicin or RTX induced desensitization to subsequent stimulation of Ca-45 uptake. The potency for desensitization by RTX in the MCs corresponded to that for Ca-45 uptake, whereas in DRGs it occurred at significantly lower concentrations corresponding to that for the high-affinity [H-3]RTX binding site. Consistent with this difference, in MCs we were unable to detect [H-3]RTX binding. Vanilloids were noncytotoxic to the MCs, in contrast to the DRGs. Although vanilloids did not cause degranulation in MCs, in the P815 clone capsaicin evoked selective interleukin-4 release. We conclude that certain MCs possess vanilloid receptors, but only the C-type that functions as a channel. Our finding that MCs can respond directly to capsaicin necessitates a reevaluation of the in vivo pathway of inflammation in response to vanilloids. This is a US government work. There are no restrictions on its use.
Tárgyszavak:	Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
Megjelenés:	Blood. - 91 : 4 (1998), p. 1332-1340. -
További szerzők:	Maurer, Marcus Modarres, Shayan Lewin, Nancy E. Brodie, Chaya Ács Géza (1939-) (traumatológus) Ács Péter Paus, Ralf Blumberg, Peter M.
Internet cím:	elektronikus változat Intézményi repozitóriumban (DEA) tárolt változat
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