Info

5.7 ± 0.58

Ala!GHRP-6+GHRH

3 + 3

88.0 ± 19.0

aBlood collected +10 (26-d-old rat), +20 (rhesus monkey), +15 (cow) min after iv peptide.

aBlood collected +10 (26-d-old rat), +20 (rhesus monkey), +15 (cow) min after iv peptide.

A series of GHRP antagonists were synthesized between 1980-83. The in vitro results of HisDTrpDLysTrpDPheLysNH2, a GHRP antagonist, and the GHRH antagonist, DArg2,Ala8915-GHRH, developed by Coy et al. are recorded in (Table 6) (26). The GHRP antagonist inhibits the GH response to GHRP but not GHRH and the GHRH antagonist inhibits GHRH but not GHRP. In 1991, certain substance P antagonists were found to inhibit the GH response to GHRP (30) as well as labeled GHRP in the pituitary GHRP RRA (31).

Clark and Robinson (32) continuously infused GHRP-6 to freely moving conscious rats over 8 h and a pulse of GHRH was administered each hour. GHRH pulses inconsistently released GH in saline treated control rats, whereas in the GHRP-6 treated rats, GH was consistently released by the pulses of GHRH. These results were interpreted to reflect a hypothalamic action of GHRP. Since exogenous GHRH was administered in this study, it is obvious that the hypothalamic action of GHRP is not due to the endogenous release of GHRH. Other results in support of a GHRP hypothalamic action include demonstration of high affinity binding studies in membranes of both the hypothalamus and pituitary by Codd et al. (33) and Sethumadhavan et al. (31) as well as those of Dickson et al. (34), who showed that by both iv and icv routes, GHRP-6 increased c-Fosproduction in select neurons of the arcuate nucleus of the hypothalamus (35,36), Guillaume et al. showed that GHRH was increased in hypophyseal portal blood of sheep following treatment with hexarelin (37). Also, results of Mallo et al. (38) demonstrated a GHRP hypothalamic site of action following hypophyseal stalk section and pituitary transplan-

Table 6

In Vitro Effects of GHRH and GHRP Competitive Antagonists on the GH Responses of GHRP and GHRH

DArg2Ala8'9'15GHRH

Table 6

In Vitro Effects of GHRH and GHRP Competitive Antagonists on the GH Responses of GHRP and GHRH

DArg2Ala8'9'15GHRH

Peptide

Dose ng/mL

Dose yig/mL

GH (ng/mL ± SEM)a

Control

179 ± 4

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