Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.21.1 (chymotrypsin)
 10,938 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Messenger RNA extracted from rat medullary carcinoma of the thyroid directs the synthesis in cell-free translation systems of a precursor of calcitonin, Mr = 15,000, substantially larger than the mature form of the hormone, Mr = 3,500. When translations of the mRNA were carried out in the presence of microsomal membranes prepared from a canine pancreas, a larger product (apparent Mr = 17,000) was observed by electrophoresis of the labeled proteins in the translation mixtures on sodium dodecyl sulfate-polyacrylamide gels. This membrane-processed product of Mr = 17,000 was specifically immunoprecipitated by an antiserum to synthetic calcitonin and bound to concanavalin A-Sepharose. Incubation of the proteins synthesized in the cell-free translations performed in the presence of microsomal membranes with the glycosidase, endo-beta-N-acetylglucosaminidase H, reduced the apparent molecular weight of the membrane-processed precursor from 17,000 to 12,000. In addition, the processed Mr = 17,000 calcitonin-related precursor, but not the initial, unprocessed precursor of Mr = 15,000, was resistant to proteolytic digestion by a mixture of trypsin and chymotrypsin. These results indicate that the biosynthesis of calcitonin involves the glycosylation and proteolytic cleavage of a newly synthesized precursor along with sequestration of the processed precursor within microsomal vesicles. Thus, the calcitonin precursor undergoes extensive co- and post-translational processing to the smaller, unglycosylated hormone that is secreted.
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PMID:Procalcitonin is a glycoprotein. 720 75

1. Nitric oxide (NO) is known from previous studies to be the principle transmitter in NANC inhibitory nerves supplying the hamster urethra. However, the identity of the cotransmitter(s) responsible for the responses remaining following block with L-NG-nitroarginine methyl ester (L-NAME) is not known. 2. Electrical field stimulation (EFS) of circular strips of hamster proximal urethra precontracted with arginine vasopressin (AVP 10(-8) M), and in the presence of phentolamine (10(-6) M), propranolol (10(-6) M) and atropine (10(-6) M), caused frequency-dependent relaxation, which was attenuated by suramin (10(-4) M) and reactive blue 2 (RB2; 2 x 10(-4) M), but not by pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid (PPADS; 10(-4) M), alpha-chymotrypsin (10-50 u ml(-1)) or by the vasoactive intestinal polypeptide (VIP) antagonist, [Lys1, Pro2,5, Arg3,4, Tyr6]-VIP, (5 x 10(-7)-10(-6) M). In the presence of indomethacin (10(-6) M) frequency-dependent relaxations to EFS were enhanced, particularly at the lower frequencies of stimulation. EFS-induced relaxation was blocked by tetrodotoxin (10(-6) M), indicating its neurogenic origin. 3. Exogenous ATP (10(-7)-10(-3) M) produced concentration-related relaxations which were attenuated by the P2-purinoceptor antagonists suramin (10(-4) M) and RB2 (2 x 10(-4) M) but not by PPADS (10(-4) M). ATP-induced relaxations were also reduced significantly by indomethacin (10(-6) M). The inhibitory responses to ATP were urothelium- and NO-independent, since they were not affected by either removal of urothelium or by L-NAME (10(-4) M). 4. Exogenous VIP (10(-9)-10(-7) M) induced concentration-related relaxations which were not affected by urothelium removal, L-NAME (10(-4) M), alpha-chymotrypsin (10-50 u ml(-1)) or by [Lys1, Pro2,5, Arg3,4, Tyr6]-VIP (3 x 10(-7)-10(-6) M). Nevertheless, suramin (10(-4) M) and RB2 (2 x 10(-4) M) but not PPADS (10(-4) M) antagonized the VIP-induced relaxant responses. Calcitonin gene-related peptide (CGRP: 10(-9)-10(-7) M) was devoid of any effect or only elicited a small relaxant response in AVP-precontracted strips. 5. Exogenous prostaglandin E2 (PGE2; 10(-9)-3 x 10(-6) M) and the NO donor, sodium nitroprusside (SNP; 10(-8)-3 x 10(-5) M) elicited concentration-related relaxations on the hamster proximal urethra which were not attenuated by suramin (10(-4) M), RB2 (2 x 10(-4) M), or by PPADS (10(-4) M), indicating a specific inhibitory effect of the antagonists used. 6. In summary, these results are consistent with the view that ATP is an inhibitory transmitter released from inhibitory nerves supplying the NANC relaxation of hamster proximal urethra. The relaxant effect of ATP is NO- and urothelium-independent. The present study did not demonstrate whether VIP is released from parasympathetic nerves during EFS, since both alpha-chymotrypsin and [Lys1, Pro2,5, Arg3,4, Tyr6]-VIP were ineffective on neurogenic responses.
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PMID:ATP and vasoactive intestinal polypeptide relaxant responses in hamster isolated proximal urethra. 972 Jul 75

Electrical field stimulation (EFS)-induced non-adrenergic non-cholinergic (NANC) relaxation responses in the rabbit vaginal wall were investigated. These NANC responses were partially inhibited with the nitric oxide synthase (NOS) inhibitors N(G)-nitro-L-arginine methyl ester (L-NAME; 500 microM), N(G)-nitro-L-arginine (300 microM) or N-iminoethyl-L-ornithine (500 microM) or the selective soluble guanylate cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3,-a]quinoxalin-1-one (ODQ, 10 microM). Application of L-NAME and ODQ concomitantly did not increase the degree of inhibition. L-NAME or ODQ were observed to be more effective at low frequencies. The resistant part of the responses was more pronounced at higher frequencies and was completely inhibited by tetrodotoxin (1 microM). Exogenous application of the peptides vasoactive intestinal peptide (VIP), pituitary adenylate cyclase activating peptide (PACAP-27 and PACAP-38), peptide histidine methionine (PHM), peptide histidine valine (PHV), helospectin-I or -II induced a relaxation response. Calcitonin gene-related peptide or substance P did not cause any relaxation. The peptidase alpha-chymotrypsin (type II; 2 units ml(-1)) did not affect non-nitrergic NANC responses, although it did inhibit relaxation responses elicited by exogenous VIP, PACAP-27, PACAP-38, PHM, PHV, helospectin-I or -II. K(+) channel inhibitors apamin (1 microM) or charybdotoxin (100 nM) when used alone or in conjunction did not affect non-nitrergic NANC responses. The non-nitrergic NANC responses were not associated with any increase in intracellular cyclic adenosine-3', 5'-monophosphate (cyclic AMP) or cyclic guanosine-3', 5'-monophosphate (cyclic GMP) concentrations. The peptide-induced relaxations were all associated with increases in cyclic AMP concentrations. These results suggest that a neuronal factor elicits non-nitrergic NANC responses in the rabbit vaginal wall. The identity of this factor remains to be established.
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PMID:Characterization of the non-nitrergic NANC relaxation responses in the rabbit vaginal wall. 1181 90

The neurotransmitters mediating relaxation of lower esophageal sphincter (LES) were studied using circular LES strips from adult pigs in organ baths. LES relaxation by sodium nitroprusside (1 nM-3 microM), vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating peptide (PACAP; 1 nM-1 microM), ATP (10 microM-30 mM), and tricarbonyldichlororuthenum dimer (1 microM-1 mM) was unaffected by tetrodotoxin (1 microM) or l-N(G)-nitroarginine methyl ester (l-NAME; 100 microM). Calcitonin gene-related peptide (CGRP; 1 nM-1 microM) did not affect LES tone. ATP relaxation was blocked by 1 microM apamin and the P2Y(1) antagonist MRS 2179 (N6-methyl 2'-deoxyadenosine 3',5'-bisphosphate; 10 microM). Apamin inhibited PACAP relaxation. VIP and PACAP relaxation was blocked by 10 U/ml alpha-chymotrypsin. L-NAME (-62.52 +/- 13.13%) and 1H-[1,2,4]oxadiazole-[4,3-alpha]quinoxalin-1-one (ODQ; 10 microM, -67.67 +/- 6.80%) similarly inhibited electrical LES relaxation, and apamin blocked non-nitrergic relaxation. Nicotine relaxation (100 microM) was inhibited by L-NAME (-60.37 +/- 10.8%) and ODQ (-41.90 +/- 7.89%), and apamin also blocked non-nitrergic relaxation. Non-nitrergic and apamin-sensitive LES relaxation by electrical stimulation or nicotine was strongly inhibited by MRS 2179, slightly inhibited by alpha-chymotrypsin and the P2X(1,2,3) receptor antagonist NF 279 (8,8 cent-[carbonylbis(imino-4,1-phenylenecarbonylimino-4,1-phenylenecarbonylimino)]bis-1,3,5-naphthalenetrisulfonic acid hexasodium salt; 10 microM), and unaffected by tin protoporphyrin IX (100 microM). Porcine LES relaxation after stimulation of intrinsic inhibitory motor neurons is mediated by two main neuromuscular pathways: nitric oxide through guanylate cyclase signaling and apamin-insensitive mechanisms and by non-nitrergic apamin-sensitive neurotransmission mainly mediated by ATP, ADP, or a related purine acting on P2Y1 receptors and a minor contribution of purinergic P2X1,2,3 receptors and PACAP. Nitrergic and purinergic co-transmitters show parallel effects of similar magnitude without major interplay. Our study shows no role for CGRP and only a minor one for VIP and carbon monoxide in porcine LES relaxation.
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PMID:Pharmacologic characterization of intrinsic mechanisms controlling tone and relaxation of porcine lower esophageal sphincter. 1630 17