title: Interaction of rat adenohypophyseal vasopressin receptors with vasopressin analogues substituted at positions 7 and 1: dissimilarity from the V1 vasopressin receptor.
abstract: We readdressed the question of whether or not rat adenohypophyseal vasopressin receptors have a ligand selectivity which is similar to that of the V1 subtype of vasopressin receptors. Vasopressin analogues substituted in positions 7 and 1 were used. By incubating rat anterior pituitary quarters or by perifusing rat isolated anterior pituitary cells, the effect of the vasopressin analogues on the release of beta-endorphin-like or adrenocorticotropin-like immunoreactivity was examined. The replacement of the proline residue in position 7 by sarcosine or N-methyl-alanine did not change the maximum effect reached but increased the EC50 values 20- or 5-fold, respectively, when compared with arginine vasopressin. This decrease in beta-endorphin-releasing activity was no longer observed after additional removal of the alpha-amino group of cysteine in position 1. Since these substitutions are known to drastically reduce vasopressor activity, these data suggest that the beta-endorphin-releasing activity of vasopressin can be dissociated from its V1 receptor activity. Vasopressin analogues substituted in position 7 and with deaminopenicillamine or beta-mercapto-beta,beta-cyclopentamethylenepropionic acid in position 1 were found to be weak antagonists of the beta-endorphin-releasing activity of vasopressin. Since these analogues are potent antagonists at the V1 receptor, these data suggest that the deaminopenicillamine and, more so, the beta-mercapto-beta,beta-cyclopentamethylenepropionic acid residues in position 1 of vasopressin are strong 'binding elements' at the V1 vasopressin receptor but weak 'binding elements' at the adenohypophyseal vasopressin receptor.(ABSTRACT TRUNCATED AT 250 WORDS)
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000378:metabolism*; D000818:Animals; D001667:Binding, Competitive; D004723:Endorphins / Q000378:metabolism*; D008297:Male; D010903:Pituitary Gland, Anterior / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011945:Receptors, Angiotensin / Q000187:drug effects* / Q000378:metabolism; D017483:Receptors, Vasopressin; D013329:Structure-Activity Relationship; D014667:Vasopressins / Q000378:metabolism / Q000494:pharmacology*; D001615:beta-Endorphin
chemical_list: D004723:Endorphins; D011945:Receptors, Angiotensin; D017483:Receptors, Vasopressin; D014667:Vasopressins; D001615:beta-Endorphin; D000324:Adrenocorticotropic Hormone