The effect of thiorphan on release of sensory neuropeptides from guinea-pig cerebral venous sinuses.
The effect of peptidase inhibitors on neuropeptide release from peripheral endings of capsaicin-sensitive sensory neurons was studied in cerebral superior sagittal and transverse sinuses of guinea-pig. Capsaicin (1 microM)-evoked release of substance P-like immunoreactivity (SP-LI) was increased in a concentration-dependent manner by thiorphan (0.1-10 microM). Captopril (10 microM) or a mixture of bestatin (10 microM), leupeptin (10 microM) and bacitracin (10 microM) did not affect the capsaicin-evoked SP-LI release. Thiorphan (10 microM) increased also the capsaicin-evoked release of neurokinin A-like immunoreactivity (TK-LI) and calcitonin gene-related peptide-like immunoreactivity (CGRP-LI) by 228% and 172%, respectively, while captopril (10 microM) was without effect. Thiorphan (10 microM), but not captopril (10 microM), enhanced by 239% CGRP-LI release induced by bradykinin (10 microM). In the cerebral venous vessels neutral endopeptidase (EC 3.4.24.11, NEP)-like activity was 58.8 +/- 6.1 pmol/mg protein/min, while angiotensin converting enzyme-like activity was below the detection limit of the assay. A thiorphan-sensitive mechanism, putatively attributable to NEP, plays a major role in the inactivation of peptides released from or acting on capsaicin-sensitive sensory fibres of cerebral venous sinuses of guinea-pig.
Tramontana
M
M
Institute of Internal Medicine IV, University of Florence, Italy.
Del Bianco
E
E
Ziche
M
M
Santicioli
P
P
Maggi
C A
CA
Geppetti
P
P
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D001920:Bradykinin / Q000494:pharmacology; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology; D002211:Capsaicin / Q000494:pharmacology; D003392:Cranial Sinuses / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D006168:Guinea Pigs; D007124:Immunoenzyme Techniques; D066298:In Vitro Techniques; D008297:Male; D009475:Neurons, Afferent / Q000378:metabolism*; D009479:Neuropeptides / Q000378:metabolism*; D011863:Radioimmunoassay; D015244:Thiorphan / Q000494:pharmacology*
D000806:Angiotensin-Converting Enzyme Inhibitors; D009479:Neuropeptides; D015244:Thiorphan; D015740:Calcitonin Gene-Related Peptide; D002211:Capsaicin; D001920:Bradykinin